과메기에서 histamine 분해능을 나타내는 세균의 분리 동정

김민우,김영만,Kim Min-Woo,Kim Young-Man 한국생명과학회 2006 생명과학회지 Vol.16 No.1

To isolate and identify histamine degrading bacteria from Kwamegi, bacteria were screened with restriction media containing histamine. Ten strains were selected through morphological and biochemical identification procedure followed by comparison with DNA sequence of 16 rRNA gene. And also, these strains were confirmed by the histamine degrading assay such as turbidity and enzymatic assay. The results of identification are as followings : Ewingella americana B791, Arthrobacter sp. R45S, Halomonas marisflava, Psychrobacter sp. 9B-7, Bacillus sp. LMC 21002, Psychrohacter cibarius BC-220, Bacillus megaterium KL-197 were identified showing homology of $99\%,\;95\%,\;98\%,\;99\%,\;99\%,\;99\%\;and\;98\%$, respectively. Three strains remain unidentified. Arthrobacter sp. R45S, H. marisflava, Bacillus sp. LMG 21002, B. megaterium KL-197 showed histamine degrading activity, whereas, Psychrobacter sp. 9B-7 only showed weak activity. Three unidentified strains also have histamine degrading activity. In contrast, E. american B791 and p. cibarius JG-220 did not show any significant activity of histamine degradation. The strains isolated from this study showed relatively fast growth rate and histamine degrading rate as compared to those from salted mackerel. 과메기에서 histamine분해능을 가진 세균을 분리 동정하기 위하여 histamine만을 첨가한 제한배지에서 균을 분리했다. 기본적인 형태 및 생화학적 동정시험을 거쳐 10종의 시험균주를 선택하여 16S rDNA 염기서열 비교에 의한 계통발생학적 분석으로 동정하였다. 동정된 세균의 histamine분해능은 탁도측정법과 효소법에 의해 재 확인하였으며 그 실험 결과는 다음과 같다. 16S rDNA 염기서열 비교에 의한 계통 발생학적 분석을 이용하여 동정한 결과, E americana B791, Arthrobacter sp. R45S, H. marisflava, P. sp. 9B-7, Bacillus sp. LMG 21002, P. cibarius JG-220, B. megaterium KL-197 7종이 동정되었고, 각각 $99\%,\;95\%,\;98\%,\;99\%,\;99\%,\;99\%,\;98\%$의 상동성을 보였으며, 3종은 미동정되었다. 동정된 세균의 histamine분해능을 탁도측정법과 효소법에 의해 재 확인한 결과, Arthrobacter sp. R45S, H. marisflava, Bacillus sp. LMG 21002, B. megaterium KL-197이 분해능을 나타내었고, Psychrobacter sp. 9B-7은 미약한 분해능을 보였으며 미동정된 3종도 분해능이 있는 것으로 나타났다. 그리고 E. americana B791과 P. cibarius JG-220은 분해능이 불확실한 것으로 확인되었다 자반고등어에서 분리한 균주보다 시험균주 모두가 생육과 histamine의 분해속도가 비교적 빨랐다.

Histamine Induced Production of Chemokine CXCL8 Through H1R/PLC and NF-κB Signaling Pathways in Nasal Fibroblasts

강병진,박주후,이흥만 대한비과학회 2020 Journal of rhinology Vol.27 No.2

Background and Objectives: Histamine has been suggested to play an important role during allergic and inflammatory reactions, affecting allergic rhinitis and chronic rhinosinusitis. CXCL8 is a pro-inflammatory chemokine and a critical factor that causes many airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.Materials and Method: Histamine cytotoxicity was measured by MTT assay. Real-time polymerase chain reaction was used to identify histamine type 1 receptor in nasal fibroblasts. The fibroblasts were then treated with histamine with or without a histamine type 1 receptor antagonist and the CXCL8 protein was assessed using an enzyme-linked immunosorbent assay (ELISA). The downstream signaling molecules, including phospholipase C and phospho-p50, were evaluated by western blot and immunofluorescent staining.Results: Histamine had no significant cytotoxic effect until the concentration reached 1,000 μM. Histamine type 1 receptor mRNA was expressed in nasal fibroblasts. CXCL8 protein expression level was significantly increased following histamine stimulation. However, the expression level of CXCL8 decreased when phospholipase C was inhibited by U73122. Histamine increased phospho-p50 expression as seen in western blot results. The BAY11-7082, NF-κB inhibitor significantly reduced CXCL8 production in histamine-stimulated nasal fibroblasts.Conclusion: Histamine can induce the production of NF-κB controlled-chemokine CXCL8 by nasal fibroblasts, which supports a role for histamine in upper airway inflammatory diseases.

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-κB Pathways in Nasal Fibroblasts

박일호,엄지영,조정선,이승훈,이상학,이흥만 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.6

Purpose: Based on the close relationship between histamine and interleukin 6 (IL-6), we hypothesized that histamine may regulate the production of cytokines, such as IL-6, during allergic inflammation. Here, we examined the role of histamine in IL-6 production and histamine receptor activity in nasal fibroblasts, along with the mechanisms underlying these effects. Methods: Experiments were performed using nasal fibroblasts from 8 normal patients. RT-PCR was used to identify the major histamine receptors expressed in nasal fibroblasts. Fibroblasts were then treated with histamine with or without histamine-receptor antagonists, and monitored for IL-6 production using an ELISA. Four potential downstream signaling molecules, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB, were evaluated by Western blot, and a luciferase reporter assay. Results: Elevated expression was seen for all histamine receptors, with IL-6 protein levels increasing significantly following histamine stimulation. Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts. Histamine increased the expression level of phosphorylated p38 (pp38), pERK, and pJNK, as well as NF-κB induction. The H1R antagonist actively suppressed pp38 and NF-κB expression in histamine-induced nasal fibroblasts, but not pERK and pJNK. The p38 inhibitor strongly attenuated IL-6 production in histamine-stimulated nasal fibroblasts. Conclusions: The data presented here suggest that antihistamines may be involved in the regulation of cytokines, such as IL-6, due to the role of histamine as an inflammatory mediator in nasal fibroblasts.

P107 : Histamine-free diet in adult patients with atopic dermatitis

( Jin Hye Kim ),( Yun Sun Byun ),( Yoon Seok Yang ),( Soo Ick Cho ),( Hye One Kim ),( Chun Wook Park ),( Cheol Heon Lee ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: In adult patients with atopic dermatitis (AD), causal relationship between food and disease exacerbation is relatively weak compared to childhood patients. However, there are many patients who report food-related aggravation of their skin symptoms, and some of them may have histamine intolerance. Objectives: The aim of this study was to evaluate the role of ingested histamine in adult AD and to investigate the effect of histamine-free diet in adult patients with AD. Methods: Adult patients with AD (18 years old or more) and healthy controls were enrolled. Foods with high amounts of histamine were prohibited to all patients for 4 weeks. No diet restriction was done to the healthy controls. Eczema area and severity index (EASI) and degree of pruritus using visual analogue scale (VAS) were evaluated. Plasma histamine levels and DAO activity were determined and compared with those of the control group. Results: Seventeen adult patients were recruited and among them, 12 completed the 4 weeks of histamine-free diet. The basal plasma histamine levels in patients and healthy volunteers showed no significant difference. The basal DAO activity was significantly higher in patients compared to that of the healthy controls. There was no significant difference in plasma histamine level after the histamin Conclusion: Ingested histamine might be unrelated with AD severity and histamine-free diet is unhelpful for adult patients with AD.

자반고등어에서 histamine 분해능을 가진 세균의 분리 동정

황수정,김영만,Hwang Su-Jung,Kim Young-Man 한국생명과학회 2005 생명과학회지 Vol.15 No.5

Histamine은 적색육 어류의 histidine이 어육 중의 Morganella morganii, Hafnia alvei 및 Klebsiella pneumoniae와 같은 부패세균에 의해 탈탄산 되어 초기에 형성되는 것으로 allergy성 식중독을 일으킬 수 있다. 이는 적색육 어류인 고등어의 선도저하 시에 많이 생성된다. 그리고 부패 후기에는 histamine을 분해하는 세균도 존재하는 것으로 알려져 있다. 그러므로, histamine 식중독의 잠재력을 지닌 자반고등어로 인한 식중독 사고 예방과 그 위생 대책을 수립하는데 필요한 자료를 얻고자 자반고등어에서 histamine 분해능을 가진 균을 분리, 동정하였다. 시료는 대형마트에서 시판되는 상태로 구입하였다. 질소원과 탄소원으로써 histamine만을 첨가한 제한배지를 사용하여 histamine 분해능을 가진 균을 분리하였다. 그리고 Cram staining, oxidase, catalase, citrate, TSI test, $H_{2}S$ reaction 및 indole 생성 등의 기본적인 생화학적 동정시험을 거쳐 10종의 시험균주를 선택하였다. 이 균주들을 16SrRNA gene 염기서열 비교에 의한 계통발생학적 분석을 이용하여 동정 하였다. 그 결과, Pseudomonas putida strain RA2, Halomonas marina, Uncultured Arctic sea ice bacterium clone ARKXV1/2-136, Halomonas venusta, Psychrobacter sp. HS5323, Pseudemonas putida KT2440, Rhodococcus erythropolis, Klebsiella terrigena (Raoultella terrigena), Alteromonadaceae bacterium T1, Shewanella massilia의 10종이 모두 동정 되 었으며, 각각 $100\%,{\;}100\%,{\;}99\%,{\;}99\%,{\;}99\%,{\;}99\%,{\;}100\%,{\;}95\%,{\;}99\%,{\;}100\%$의 상동성을 보였다. Histamine분해능의 존재를 탁도측정법과 효소법에 의해 확인한 결과, 분리된 10종 모두의 histamine 분해능이 재확인 되었고, 그 중 Shewanella massilia가 최대의 histamine 분해능을 보이는 것으로 확인되었다. 이 결과로 자반고등어 시판 제품에는 다수의 histamine 분해 세균이 존재하는 것을 확인할 수 있었으며, 이 세균을 활용한다면 식품 내 존재하는 histamine을 효과적으로 분해할 수 있을 것이라 예상된다. Histamine can be produced at early spoilage stage through decarboxylation of histidine in red-flesh fish by Proteus morganii, Hafnia alvei or Klebsiella pneumoniae. Allergic food poisoning is resulted from the histamine produced when the freshness of Mackerel degrades. Conversely it has been reported that there are bacteria which decompose histamine at the later stage. We isolated histamine decomposers from salted mackerel and studied the characteristics to help establish hygienic measure to prevent outbreak of salted mackerel food poisoning. All the samples were purchased through local supermarket. Histamine decomposers were isolated using restriction medium using histamine 10 species were selected. Identification of these isolates were carried out by the comparison of 16S rDNA partial sequence; as a result, we identified Pseudomonas putida strain RA2 and Halomonas marina, Uncultured Arctic sea ice bacterium clone ARKXV1/2-136, Halomonas venusta, Psychrobacter sp. HS5323, Pseudomonas putida KT2440, Rhodococcus erythropolis, Klebsiella terrigena (Raoultella terrigena), Alteromonadaceae bacterium T1, Shewanella massilia with homology of $100\%,{\;}100\%,{\;}99\%,{\;}99\%,{\;}99\%,{\;}99\%,{\;}100\%,{\;}95\%,{\;}99\%,{\;}and{\;}100\%$respectively. Turbidometry determination method and enzymic method were employed to determine the ability of histamine decomposition. Among those species Shewanella massilia showed the highest in ability of histamine decomposition. From these results we confirmed various histamine decomposer were present in salted mackerel product in the market.

P237 : A study of histamine content in Korean traditional foods

( Yun Sun Byun ),( Yong Se Cho ),( Yoon Seok Yang ),( Jin Hye Kim ),( Bo Young Chung ),( Hye One Kim ),( Chun Wook Park ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Ingestion of foods that contain much histamine can provoke not only signs and symptoms of histamine poisoning such as nausea, vomiting, and diarrhea, but also allergic reactions such as rash and pruritus. Objectives: The purpose of this study is to present a list of Korean traditional foods containing great amounts of histamine. Methods: The histamine level of foods was measured by using enzyme-linked immunosorbent assay (ELISA). Results: Fermented pastes, such as soybean paste (1164 ng/g) and red pepper paste (1448 ng/g), showed high histamine levels. There wasn’t no difference in histamine level depending on cooking methods, such as boiling. Fermented cabbage (378 ng/g) and radish (500 ng/g), such as kimchi, showed 30 to 50 times higher histamine levels than the ones of fresh cabbage (11 ng/g) and fresh radish (10 ng/g). Salty fermented anchovies showed high histamine levels (1157 ng/g), but salty fermented shrimps (27 ng/g) showed low histamine levels, as did fresh shrimps (24 ng/g). Conclusion: We suggest that this study is used as a guideline for educational dietary interventions for patients with chronic urticaria or histamine intolerance.

A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic Spontaneous Urticaria

Son, Jee Hee,Chung, Bo Young,Kim, Hye One,Park, Chun Wook 대한피부과학회 2018 Annals of Dermatology Vol.30 No.2

<P><B>Background</B></P><P>In adult patients with chronic urticaria (CU), the prevalence of food allergy is low compared to childhood patients. However, there are many patients who report food-related aggravation of CU, and some of them may have histamine intolerance.</P><P><B>Objective</B></P><P>The aim of this study was to evaluate the role of ingested histamine and to investigate the effect of a histamine-free diet in adult patients with CU.</P><P><B>Methods</B></P><P>Twenty-two adult patients with CU were enrolled. Foods with high amounts of histamine were prohibited to all patients for four weeks. The degree of severity of the urticaria was evaluated using the urticaria severity score (USS) and urticaria activity score (UAS). Plasma histamine levels and diamine oxidase (DAO) activity were determined and compared before (baseline) and after the histamine-free diet.</P><P><B>Results</B></P><P>Twenty-two adult patients were recruited and completed four weeks of histamine-free diet. The USS and UAS scores each showed significant differences before and after the histamine-free diet (<I>p</I>=0.010, <I>p</I>=0.006). There was a significant reduction in plasma histamine level after the histamine free-diet, compared with baseline (<I>p</I>=0.010). However, DAO activity did not change after the histamine-free diet (<I>p</I>=0.165).</P><P><B>Conclusion</B></P><P>Our study suggested that ingested histamine might be related to CU severity and that a histamine-free diet is helpful for treatment of adult patients with CU.</P>

Effect of Different Cooking Methods on Histamine Levels in Selected Foods

( Bo Young Chung ),( Sook Young Park ),( Yun Sun Byun ),( Jee Hee Son ),( Yong Won Choi ),( Yong Se Cho ),( Hye One Kim ),( Chun Wook Park ) 대한피부과학회 2017 Annals of Dermatology Vol.29 No.6

Background: Histamine in food is known to cause food poisoning and allergic reactions. We usually ingest histamine in cooked food, but there are few studies about the influence of cooking method on the histamine level. Objective: The purpose of this study was to determine the influence of cooking methods on the concentration of histamine in foods. Methods: The foods chosen were those kinds consumed frequently and cooked by grilling, boiling, and frying. The histamine level of the food was measured using enzyme-linked immunosorbent assay. Results: Grilled seafood had higher histamine levels than raw or boiled seafood. For meat, grilling increased the histamine level, whereas boiling decreased it. For eggs, there was not much difference in histamine level according to cooking method. Fried vegetables had higher histamine levels than raw vegetables. And fermented foods didn’t show much difference in histamine level after being boiled. Conclusion: The histamine level in food has changed according to the cooking method used to prepare it. Frying and grilling increased histamine level in foods, whereas boiling had little influence or even decreased it. The boiling method might be helpful to control the effect of histamine in histamine-sensitive or susceptible patients, compared with frying and grilling. (Ann Dermatol 29(6) 706∼714, 2017)

FCP 10 Effect of histamine-free diet in adult patients with chronic urticaria

( Jee Hee Son ),( Yong Won Choi ),( Yong Se Cho ),( Yun Sun Byun ),( Bo Young Chung ),( Hye One Kim ),( Hee Jin Cho ),( Chun Wook Park ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

Background: In adult patients with chronic urticaria (CU), causal relationship between food and disease exacerbation is relatively weak compared to childhood patients. However, there are many patients who report food-related aggravation of CU, and some of them may have histamine intolerance. Objectives: The aim of this study was to evaluate the role of ingested histamine and to investigate the effect of histamine-free diet in adult patients with CU. Methods: Twenty-two adult patients with CU were enrolled. Foods with high amounts of histamine were prohibited to all patients for 4 weeks. Department of nutrition supplied the reference menu with histamine-free diet and consulted the patients. Severity degree of urticaria using Urticaria Severity Score (USS) and Urticaria Activity Score (UAS) were evaluated. Plasma histamine levels and diamine oxidase (DAO) activity were determined and compared between baseline and after the histamine-free diet. Results: Twenty-two adult patients were recruited and completed the 4 weeks of histamine-free diet. There was a significant difference in plasma histamine level between baseline and after the histamine free-diet (p=0.014). DAO activity did not change after the histamine-free diet (p=0.165). Likewise, both USS and UAS score significantly decreased after the histamine-free diet (p=0.010, p=0.006). Conclusion: Ingested histamine might be related with CU severity and histamine-free diet is helpful for adult patients with CU.

Airways are More Reactive to Histamine than to Methacholine in Patients with Mild Airway Hyperresponsiveness, Regardless of Atopy

( In Seon S. Choi ),( Seok Lee ),( Dae Hyeon Kim ),( Se Woong Chung ),( Yoon Cheol Lee ),( Jae Yeong Cho ),( Woo Jin Lee ) 대한내과학회 2007 The Korean Journal of Internal Medicine Vol.22 No.3

Background: The airway muscles from allergen-sensitized animals in vitro show a heightened response to histamine, but not to carbachol. This study investigated whether the airway responsiveness to histamine in vivo is comparable to that of methacholine in human subjects with varying degrees of atopy. Methods: One-hundred-and-sixty-eight consecutive adult asthma patients or volunteers underwent bronchoprovocation tests to both histamine and methacholine after determining their blood eosinophil counts, serum total IgE levels and skin test reactivity to 10 common aeroallergens. Results: The responsiveness to histamine was significantly related to that to methacholine (r=0.609, p<0.001), but many individuals with a negative methacholine test response showed a positive response to histamine. The histamine-bronchial reactivity index (BRindex) was significantly higher than the methacholine-BRindex in subjects with a positive response to none (n=69, p<0.01) or only one (n=42, p<0.001) of histamine and methacholine, while there was no significant difference in the subjects with positive responses to both of them (n=57). The histamine-BRindex was significantly higher than the methacholine-BRindex in the subjects with mild histamine hyperresponsiveness (n=58, 1.28 ±0.01 vs. 1.20±0.02, respectively, p<0.001). Both histamine and methacholine responsiveness was significantly related to the atopy markers. However, the histamine-BRindex/methacholine-BRindex ratio of the atopics was not significantly different from that of the non-atopics. Conclusions: The airway responsiveness to histamine is comparable to that of methacholine in the subjects with positive responses to both histamine and methacholine, but the airway responsiveness to histamine is greater than that to methacholine in those subjects with mild airway hyperresponsiveness, regardless of atopy.