Immunomodulatory biomaterials for implant-associated infections: from conventional to advanced therapeutic strategies

Dong Jiale,Wang Wenzhi,Zhou Wei,Zhang Siming,Li Meng,Li Ning,Pan Guoqing,Zhang Xianzuo,Bai Jiaxiang,Zhu Chen 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Implant-associated infection (IAI) is increasingly emerging as a serious threat with the massive application of biomaterials. Bacteria attached to the surface of implants are often difficult to remove and exhibit high resistance to bactericides. In the quest for novel antimicrobial strategies, conventional antimicrobial materials often fail to exert their function because they tend to focus on direct bactericidal activity while neglecting the modulation of immune systems. The inflammatory response induced by host immune cells was thought to be a detrimental force impeding wound healing. However, the immune system has recently received increasing attention as a vital player in the host’s defense against infection. Anti-infective strategies based on the modulation of host immune defenses are emerging as a field of interest. This review explains the importance of the immune system in combating infections and describes current advanced immune-enhanced anti-infection strategies. First, the characteristics of traditional/conventional implant biomaterials and the reasons for the difficulty of bacterial clearance in IAI were reviewed. Second, the importance of immune cells in the battle against bacteria is elucidated. Then, we discuss how to design biomaterials that activate the defense function of immune cells to enhance the antimicrobial potential. Based on the key premise of restoring proper host-protective immunity, varying advanced immune-enhanced antimicrobial strategies were discussed. Finally, current issues and perspectives in this field were offered. This review will provide scientific guidance to enhance the development of advanced anti-infective biomaterials.

Modulation of Humoral and Cell-Mediated Immunity Against Avian Influenza and Newcastle Disease Vaccines by Oral Administration of Salmonella enterica Serovar Typhimurium Expressing Chicken Interleukin-18

Rahman, Md Masudur,Uyangaa, Erdenebileg,Eo, Seong Kug The Korean Association of Immunobiologists 2013 Immune Network Vol.13 No.1

Interleukin-18 (IL-18) has been known to induce interferon-${\gamma}$ (IFN-${\gamma}$) production and promote Th1 immunity. Although mammalian IL-18 has been characterized in great detail, the properties and application of chicken IL-18 remain largely uninvestigated as of yet. In this study, we evaluated the immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza (AI) and Newcastle disease (ND) vaccines. After oral administration of S. enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted using the same protocol 7 days later. Humoral and cell-mediated immune responses were evaluated in terms of HI antibody titers and proliferation and mRNA expression of IFN-${\gamma}$ and IL-4 of peripheral blood mononuclear cells (PBMC) in response to specific antigen stimulation. According to our results, oral administration of S. enterica serovar Typhimurium expressing chIL-18 induced enhanced humoral and Th1-biased cell-mediated immunity against AI and ND vaccines, compared to that of chickens received S. enterica serovar Typhimurium harboring empty vector. Therefore, we conclude that our proposed vaccination regimen using inactivated AI and ND viruses along with oral administration of S. enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in protecting chicken from currently circulating AI and ND virus strains.

친환경 소재 개발을 위한 유자에서의 효율적 Limonene 추출 및 면역기능 조절활성에 관한 연구

안종호 ( Ahn Jong-ho ),임현희 ( Lim Hyun-hee ),황성구 ( Hwang Seong-gu ),남인식 ( Nam In-sik ) 한국유기농업학회 2020 韓國有機農業學會誌 Vol.28 No.4

The objectives of this study were to find out the best condition of extracting methods of limonene from citron and to determine effects of limonene on immune modulation activity by measuring cytokine secretion using RAW 264.7 mouse macrophage cells. When distilled water was used as a solvent instead of organic solvents to extract limonene from citron, addition of refluxing process to simultaneous steam distillation extraction method was found to be much effective in extracting limonene. However, it required longer extraction time than using other organic solvents. Limonene extracts showed increased IL-β and IL-6 but decreased the TNF-α gene expression in limonene concentration dependant manner. However oral administration of limonene extracts to mice did not influence significantly compared to control in in vivo experiment. It might be due to that the mice were kept in well controlled and complete environment. Limonene, a natural material from citron has been approved to have a immune-modulation activity in the present study and have a potential as a feed additive that is environmentally friendly and no harmful. Further study with protected limonene, for example, for the protection of limonene from oxidation or bypass the ruminal degradation in order consequently to increase immune-modulation activity might be useful as a further research.

Perspectives on Mesenchymal Stem Cells: Tissue Repair, Immune Modulation, and Tumor Homing

홍현숙,Youngsook Son,김영훈 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.2

Mesenchymal stem cells (MSCs) or MSC-like cells have been identified in a variety of different tissues that share molecular expression profiles and biological functions but also retain a unique differentiation preference depending on their tissue origins. MSCs play beneficial roles in the healing of damaged tissue by directly differentiating to many different resident cell types and/or by secreting several trophic factors that aid tissue repair. Aside from MSCs’ reparative stem cell function, they drive immune responses toward immunosuppression and anti-inflammation. This novel function of MSCs opens up new avenues for clinical development of MSC immune-therapeutics to treat uncontrollable, life threatening, severe, chronic inflammation and autoimmune disease. Unexpectedly high rates of MSCs’ tumor homing capacity and their tumor supporting capability have also been noted in tumor-bearing animal models. In this review, we will discuss MSCs’ basic cell biology and perspectives on MSCs in terms of tissue repair, immune modulation, and tumor homing.

Placenta-derived stem cells regulates trophoblast cell invasion through immune modulation: potential implication for women with implantation failure

Gi Jin Kim 한국발생생물학회 2010 한국발생생물학회 학술발표대회 Vol.29 No.-

Implantation of the blastocyst into the maternal endometrium, mediated by well-differentiated primary cells of the placenta known as trophoblasts, grow in an invasive via complicated interaction with immune cells in the maternal myometrium. Placenta-derived stem cells (PDSCs), which is a fetal origin, display multi-lineages differentiation potential, and they are free of ethical concerns, easily accessible, abundant, and strongly immunosuppressive. However, the efficiency of PDSCs according to trophoblast invasion or immune modulation in implantation has not yet been evaluated. Here, we investigated the effects of PDSCs for trophoblast invasion as well as their potential for immune modulation of activated T cells when they co-cultured with PDSCs. Activated T cells and HTR-8SV/neo trophoblast cells were co-cultured with PDSCs according to cell dose-dependent manner. Activities for proliferation of T cells were analyzed by BrdU incorporation assay and cell invasions were estimated. Activation of T cells was significantly decreased in the group co-cultured with PDSCs comparing to normal fibroblast cells (p<0.05). In addition, trophoblast invasion by PDSCs have recorded a twofold increase than the normal fibroblast cells. These results contribute to our understanding of the potential roles of PDSCs, including immune modulation effects for trophoblast invasion in pregnancy, and provide a foundation for the development of new cell therapy-based strategies for the treatment of women with implantation.

흰점박이꽃무지 유충 추출물의 RAW264.7 세포 활성화에서 TLR4-JNK/NF-κB 신호전달 경로의 관여

박주휘,채종범,이준하,한동엽,남주옥 한국응용생명화학회 2023 Journal of Applied Biological Chemistry (J. Appl. Vol.66 No.-

In the environment in which humans live, there are various antigens that invade the human body and interfere with humans leading a healthy life, so the immune system recognizes the antigen then removes them through a complex mechanism. Macrophages are widely distributed immune cells involved in the innate immune system, and produce various immune modulators such as inducible nitric oxide synthase-induced nitric oxide, cyclooxygenase-2 induced prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor-alpha. On the other hand, Protaetia brevitarsis seulensis larvae are a type of edible insect that have emerged as an alternative to the future food supply problem. The immuno-modulatory effect through the activation of murine macrophage RAW264.7 cell via mitogen-activated protein kinases (MAPKs)/nuclear factor-kappa B (NF-κB) signaling pathways has been reported. Based on this report, in this study, we confirmed how the expression of immune modulators induced by Protaetia brevitarsis seulensis larvae extracts in RAW264.7 cells was changed by treatment with pharmacological inhibitors of tolllike receptor 4 (TLR4), MAPKs and NF-κB signaling pathways. As a result, reduction of immune modulators was confirmed in the c-Jun N-terminal kinase (JNK) inhibitor treatment group and NF- κB inhibitor treatment group among the Protaetia brevitarsis seulensis larvae-treated RAW264.7 cell. Furthermore, in the TLR4 inhibitor-treated group, decreases in phosphorylation of JNK and NF-κB factors were confirmed in Protaetia brevitarsis seulensis larvae-treated RAW264.7 cell, as well as decreases in immune modulators. This results suggest that Protaetia brevitarsis seulensis larvae activates RAW264.7 cells by the engagement of TLR4- JNK/NF-κB signaling pathway.

Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic

Iqra Mir,Sania Aamir,Syed Rizwan Hussain Shah,Muhammad Shahid,Iram Amin,Samia Afzal,Amjad Nawaz,Muhammad Umer Khan,Muhammad Idrees 질병관리본부 2022 Osong Public Health and Research Persptectives Vol.13 No.2

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

Immune-Modulating Muti-Functional Protein Nanoparticles for Enhanced Liver Cancer Therapy

A Hyung JEONG,Boram SON,Hee Ho PARK 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.10

Immune Modulation Effect of Pig Placenta Extracts in a Mouse Model: Putative Use as a Functional Food Supplement

박현정,서한극,김진회,장애라,정현정,이성대,하우태,이란,김지혁,김상호,성시흥,문상호,김보경,송혁 한국축산식품학회 2011 한국축산식품학회지 Vol.31 No.5

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4,37, 60, 80, and 100oC) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at 80oC for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 μM/105cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-α (TNF-α) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-1β (IL-1β) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-γ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

Immune Modulation Effect of Pig Placenta Extracts in a Mouse Model: Putative Use as a Functional Food Supplement

Park, Hyun-Jung,Suh, Han-Geuk,Kim, Jin-Hoi,Jang, Ae-Ra,Jung, Hyun-Jung,Lee, Sung-Dae,Ha, Woo-Tae,Lee, Ran,Kim, Ji-Hyuk,Kim, Sang-Ho,Sung, Si-Heung,Moon, Sang-Ho,Kim, Bo-Kyung,Song, Hyuk Korean Society for Food Science of Animal Resource 2011 한국축산식품학회지 Vol.31 No.5

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.