Up - Regulation of Interleukin - 4 Receptor Expression by Interleukin - 4 and CD40 Ligation via Tyrosine Kinase - Dependent Pathway

( Hyun Il Kim,Eui Young So,Suk Ran Yoon,Mi Young Han,Choong Eun Lee ) 생화학분자생물학회 1998 BMB Reports Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

Kim, Hyun-Il,So, Eui-Young,Yoon, Suk-Ran,Han, Mi-Young,Lee, Choong-Eun Korean Society for Biochemistry and Molecular Biol 1998 Journal of biochemistry and molecular biology Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

인간 유방암 MDA-MB-231 세포에서 Peptide H에 의한 IL-6 발현 억제효과

성대일,박잠언,김한복,Sung, Dae Il,Park, Jameon,Kim, Han Bok 한국미생물학회 2014 미생물학회지 Vol.50 No.3

암, 류마티스, 크론병 등은 만성염증과 관련되어 있다. Interleukin-6 (IL-6)는 염증의 주요 매개인자이다. 청국장은 콩 발효식품으로 대두단백질이 분해되어 다양한 peptide가 생성되면서, 생리활성물질이 될 수 있다. 본 연구에서는 청국장에서 분리한 peptide (Gly-Val-Tyr-Tyr-Met-Tyr)를 가공한 6mer H, [(Glu-Val-Tyr-Tyr-Met-Tyr(EVYYMY)]가 유방암세포 MDA-MB-231에서 IL-6 발현을 억제할 수 있는지 여부를 결정하였다. MDA-MB-231 세포에 peptide H를 처리해 주면, IL-6 발현은 peptide를 처리하지 않은 control에 비해, 크게 억제되었으며, 세포의 성장은 농도의존적으로 억제되었다. 암 이외에, 류마티스, 크론병 등 만성염증 질환에서 IL-6 신호의 차단은 염증개선에 유효한 것으로 알려져 있다. Peptide H는 염증과 관련된 IL-6 발현의 감소효과가 있으므로, IL-6 관련 암, 류마티스, 크론병 등의 치료제 개발로 응용, 연결될 수 있을 것이다. Chronic inflammation is involved in cancers, rheumatoid arthritis, and Crohn's disease. Inerleukin-6 (IL-6) plays major roles in inflammation. Chungkookjang, fermented soybean contains diverse peptides produced by cleavage of soybean proteins. The peptides can be bioactive compounds. Peptide (Gly-Val-Tyr-Tyr-Met-Tyr was purified from Chungkookjang, and modified to be 6mer H, Glu-Val-Tyr-Tyr-Met-Tyr (EVYYMY). Peptide H's activity to suppress IL-6 expression in a human breast cancer cell, MDA-MB-231 was determined. IL-6 Expression was reduced in the cell treated with peptide H 25 times less than controls which were not treated with peptide H. Proliferation of MDA-MB-231 cells was inhibited by peptide H, which is concentration-dependent. Blocking of IL-6 signals is known to be effective in reducing inflammation in rheumatoid arthritis, Crohn's disease, and cancers. Since peptide H can reduce inflammatory IL-6 expression, application of this study will contribute to drug development for diseases which are caused by excessive IL-6.

담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

Lee, Choong-Eun,Kim, Hyun-Il,So, Eui-Young,Yoon, Suk-Ran,Han, Mi-Young The Korea Science and Technology Center 1998 BMB Reports Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis

Jo, Sungsin,Wang, Sung Eun,Lee, Young Lim,Kang, Suman,Lee, Bitnara,Han, Jinil,Sung, Il-Hoon,Park, Ye-Soo,Bae, Sang-Cheol,Kim, Tae-Hwan BioMed Central 2018 Arthritis research & therapy Vol.20 No.-

<P><B>Background</B></P><P>IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS.</P><P><B>Methods</B></P><P>TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA. Bone tissue samples were obtained at surgery from the facet joints of ten patients with AS and ten control (Ct) patients with noninflammatory spinal disease. The functional relevance of IL-17A, biological blockades, Janus kinase 2 (JAK2), and non-receptor tyrosine kinase was assessed in vitro with primary bone-derived cells (BdCs) and serum from patients with AS.</P><P><B>Results</B></P><P>Basal levels of IL-17A and IL-12/23 p40 in body fluids were elevated in patients with AS. JAK2 was also highly expressed in bone tissue and primary BdCs from patients with AS. Furthermore, addition of exogenous IL-17A to primary Ct-BdCs promoted the osteogenic stimulus-induced increase in ALP activity and mineralization. Intriguingly, blocking IL-17A with serum from patients with AS attenuated ALP activity and mineralization in both Ct and AS-BdCs by inhibiting JAK2 phosphorylation and downregulating osteoblast-involved genes. Moreover, JAK2 inhibitors effectively reduced JAK2-driven ALP activity and JAK2-mediated events.</P><P><B>Conclusions</B></P><P>Our findings indicate that IL-17A regulates osteoblast activity and differentiation via JAK2/STAT3 signaling. They shed light on AS pathogenesis and suggest new rational therapies for clinical AS ankylosis.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s13075-018-1582-3) contains supplementary material, which is available to authorized users.</P>

1995년 地方選擧와 1996년 總選擧의 比較硏究 : 政黨別 投票成向을 中心으로 Citizens' Voting Propensity To Each Political Party

韓貞一 建國大學校 社會科學硏究所 1997 社會科學論叢 Vol.2 No.-

There may be some difficulties in comparing 1995 Local Election and 1996 National Election in that the former was for electing govermors in localities (i.e., govermors in large-units, small-units, and provinces) while the latter was for electing national congressmen. Nevertheless of such limit performing a comparative analysis on issues surrounding citizens' voting behavior as found in the two elections would provide meaningful lessons for us to understand dynamic and, somehow, turbulent political processes in Korea. The main objective of this study is to illuminate the reasons why the two elections produced contradictory results in such a ahort interim period (i.e., 10 months) of the two elections. In the 1996 Fifteenth National Assembly Election, Sin-Han-Kuk Dang gained 139 seats, which shows a great reduction from 170 secured in the Fourteenth National Assembly. Whereas Kuk-Min-Howi won 79 seats in the Fifteenth National Assembly increased from 54 they gained in the Fourteenth National Assembly. Min-Joo-Dang, who cried for clearing off of 3 Kims (Kim, Young-Sam, Kim, Dae-Jung, Kim, Jong-Pil) from the stage of Korean Politics, became about being collapsed as a result of that election. Whereas Cha-Min-Ryon led by Mr. Kim, Jong-Pil ensured significant number of seats, enjoin great strides. To our surprising among others the ruling party (Sin-Han-Kuk Dang) won over opposition parties in Seoul area - the capital city of Korea - in the Fifteenth National Election, which was rarely expected. It presents a sharp contrast to the 1995 Local Election when the opposition party won an overwhelming victory over the ruling party. Reviewing specific results of the 1995 Local Election, 33.8% of the total voters supported the ruling party, Min-Ja Dang - old name of Sin-Han-Kuk Dang. Min-Joo Dang whech used to be the biggest opposition party, polled 30.5% of total votes, whereas Ja-Min-Ryon led by Mr. Kim, Jong-Pil, obtained 10.9%. Inthe 1996 National Assembly Election, the ruling party (Sin-Han-Kuk Dang) was supported by 34.5% of total voters. Sae-Jeong-Chi Kuk-Min-Howi, the biggest opposition party, obtained 25.3% of voters while Tong-Hab-Min Joo Dang and Ja-Min-Ryon gained 11.2% abd 16.2% respectively. The total number of parliamentary seats the ruling party obtained was 139 out of 299 total seats, lacking a majority in the Assembly. In electing provincial governors in the Fourteenth Election, the ruling party (Min-Ja Dang) gained 20.7% of votes, while Min-Joo Dang obtained 42.4%. In electing governors of city, district, or county Min-Ja Dang polled 35.1%, while Min-Joo Dang was supported by 47.9% of voters. In electing city or provincial assembly members Min-Ja Dang gained 36.7% of support whereas Min-Joo Dang polled 48.6% of voters. It was called a sweeping victory of the opposition party (Min-Joo Dang) in the 14th election. Citizens' voting propensity appeared in the two elections is particularly worth to be concerned: because the result of the Fifteenth Election demonstrated opposite phenomenon to that of the fourteenth Election. In the Fifteenth Election, the ruling party (Sin-Han-Kuk Dang) was supported by 36.5% of total voters, the first opposition party (Sae-Chung-Chi Kuk-Min-Hoei) was voted for by 35.2% of the total voters, and the Tong-Hab Min-Joo Dang gained only 13.5% of support. In particular, among total 47 parliamentary seats available for Seoul area, Sin-Han-Kuk Dang won 27 seats, the first opposition party(Sae-Jeong-Chi Kuk-Min Hoi) gained 18 seats, and Tong-Hab Min-Joo Dang gained only 1 seat. This means a crushing defeat of opposition parties, especially, the Sae-Jeong-Chi Kuk-Min Hoi led by Mr. Kim, Dae-Jung. This result encouraged the ruling party (Sin-Han-Kuk Dang) to be feel easy to restore a majority position in the National Assembly. As was witnessed in other elections citizens' voting propensity in the Fifteenth election also was greatly associated with party identification tied in locality. Yet, the result of the Fifteenth Election reflects that there should be something different factors associated with voters' decisions in Seoul. The reasons for such miserable defeat of the opposition parties in that election are as follows: First, the split of the Min-Joo Dang lowered the chance of being elected in each district in Seoul. The split was caused by two conflicting political forces - members in one group following Mr. Lee, Ki-Tack who tried to maintain the party (Min-Joo Dang) and the other led by Mr. Kim, Dae-Jung who broke the party to form a new political party named Sae Jeong Chi Kuk-Min Heoi. The split of the Min-Joo Dang divided voters who otherwise would had voted for the old Min-Joo Dang. The party split conduced to only 19 out of 47 winners in Seoul, even though about 48.7% of total electorates in Seoul voted for either Mr. Lee's new Min-Joo Dang or the Kim's Sae Jeong Chi Kuk-Min Heoi. This means that were it not demolished the old Min-Joo Dang would won 43 seats out of total 47 seats in Seoul area. Second, the infiltration event of North Korean armed agents into the DMZ (Demilitarized Zone) happened in the election season was deliberately exaggerated by the present government and news media in the hand of ruling parties. It led a great number of voters, who have strong aspiration for peace and safety in Korean peninsular, to vote for ruling party (Sin-Han-Kuk Dang) with little exceptions. Third, there was a lower level of voters' turnout(63.9%). In particular, the turnout rate of younger voters was very low (44.1%). The low level of younger generation's political participation is associated with high level of mistrust and apathy on ‘new conservatism’tendency of existing political parties including Sae-Chung-Chi Kuk-Min Heoi. It also has been accelerated by a recently salient backlash movement against political ideology. The lower level of turnout is absolutely unfavorable to opposite parties because, in tradition, younger voters are shown to be more likely to bo progressive and vote for opposite parties rather than conservative parties (i.e., ruling parties). Voting behavior appeared in the both elections, as stated above, should matter much to he forthcoming 1997 presidential election. The ruling party led by Mr. Kim, Young-Sam, which has been self-praised as the ‘first civilian government’in Korean history, secured majority in the legislature through demolishing opposition party and ‘majority-opposition versus minority-ruling party’political power system backed by the people in the 1995 election. In the end the ruling party rushed “labor law”and “security law”bills through the legislature by surprise on 6 o'clock, A.M. in 1996, 12/26. Inaddition, we have good reason to question about the will of the President in office and his Cabinet in dealing with the bankrupt of Han-Bo company that has been benefitted by illegal preferential financing. Han-Bo company committed the absurdity and irrationality to pull the astronomical amout of money (5 trillion 7 thousand billion won) mostly during the era of Y.S. (Kim, Young-Sam)'s presidency.It is a typical example of the corruption of government-business collusion. People believe that the present government and the President in office are not capable of resolving such a wicked anti-democratic government-business connection because of his own political weakness. It is clear that the President in office - Mr. Kim, Young-Sam - cannot keep himself to stand in politically neutral position in executing future national policies and in the forthcoming 1997 presidential election. In words, the present government failed in differentiating itself from ones of ‘notorious’military despotism that have governed Korea in outrageous ways during the past three decades in administering the affairs of state. Again, this phenomenon is attributed to the irresponsibility and the incapability of the President in office and his fellowmen. Finally, it should be noted that the manipulation of press by the party in power is another serious facet of the corruption. All successive governors have tried to use the press for their own interest with no exceptions. They have forced the press to be committed to the corruption for their own interest. This may be termed as “government-press collusion.”Many evidences supporting this argument have been disclosed in a variety of ways in most sectors in our society. Most Koreans worry about that the press will be a help to the President in office and ruling parties in the next election too.

1995~96년도 전국 모성사망원인 조사

박정한,서경,박문일,박중신,한영자,도세록 한국모자보건학회 1999 한국모자보건학회지 Vol.3 No.2

Early Phase of UVB - induced GM - CSF Upregulation in Epithelial Cell Line is not Totally Dependent on IL - 1α

Park, Kyoung Chan,Kim, Kyu Han,Ahn, Jong Seong,Chung, Jin Ho,Youn, Jai Il,Whang, Ji Hwan,Youn, Sang Woong,Kim, Young Gull,Koh, Woo Seok,Jung, Hyun Chae 대한피부과학회 1997 Annals of Dermatology Vol.9 No.4

Backgrounds : It was demonstrated that ultraviolet(UV) B light induces the release of IL-la in cultured human epithelial cell line and augmentation of GM-CSF production by UVB is reported to be mediated by IL-1α in the murine keratinocyte cell line Pam 212. Objective : The purpose of this study was to evaluate the effects of UVB on kinetic profile of IL-1 and GM-CSF mRNA expression and to see whether synthesis of GM-CSF by UVB can be completely inhibited by blocking IL-1α mediated pathway. Method : We used a competitive RT-PCR for measuring cytokine gene expression in epithelial cell line after UV radiation. Results : The IL-1α mRNA increased as early as 1h after UV irradiation, and then decreased at 3h after the irradiation. Thereafter, the response of IL-1α mRNA was upregulated with a second peak at 6h after the UV irradiation. However, mRNA for GM-CSF increased at 1h after UV light exposure and anti-IL-1α antibodies could only partially inhibit UV-augmented GMCSF production. Conclusion : UVB induced GM-CSF production seemed to be mainly mediated by UVB induced IL-1α but these results suggest that UVB may also induce GM-CSF production through an IL-1α independent pathway.

Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>