IL-37 is protective in allergic contact dermatitis through mast cell inhibition |
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Affiliation: | 1. Université de Tunis El Manar, Faculty of Medicine of Tunis, Tunisia;2. Unit Research “12SP15”: “Homeostasis and Cell Dysfuncyion”, Tunisia;3. Division of Pulmonology, Department of Paediatric and Respiratory Diseases, Abderrahmane Mami Hospital, Ariana, Tunisia;4. Pasteur Institute of Tunis, Place Pasteur, Tunisia;1. Department of Emergency, Xi''an Children''s Hospital, Xi''an 710003, Shaanxi, China;2. Department of Neonatal Intensive Care Unit, Xi''an Children''s Hospital, Xi''an 710003, Shaanxi, China;3. Department of Central Laboratory, Xi''an Children''s Hospital, Xi''an 710003, Shaanxi, China;1. Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, People''s Republic of China;2. Department of Otorhinolaryngology, Dazhou Central Hospital, Dazhou, Sichuan, People''s Republic of China;1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Department of Cardiology, the People''s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China;3. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China;4. Department of Cardiology, Handan First Hospital, Handan 056002, China;5. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China;6. Department of Cardiology, Huadu District People''s Hospital of Guangzhou, Guangzhou 510800, China |
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Abstract: | Allergic contact dermatitis (ACD), characterized predominantly by erythema, vesiculation, and pruritus, is a T cell-mediated skin inflammatory condition. Among immune cells involved in ACD, mast cells (MCs) play an essential role in its pathogenesis. As an inhibitor of proinflammatory IL-1 family members, interleukin 37 (IL-37) has been shown to ameliorate inflammatory responses in various allergic diseases. In this study, we assessed the immunomodulatory effect of IL-37 on allergic inflammation using a 2,4-dinitrofluorobenzene (DNFB)-induced ACD rat model and isolated rat peritoneal mast cells (RPMCs). Systematic application of IL-37 significantly relieved ear swelling, reduced inflammatory cell infiltration, decreased inflammatory cytokine production (TNF-α, IL-1β, IFN-γ, and IL-13), inhibited MC recruitment, lowered IgE levels, and reduced IL-33 production in the local ear tissues with DNFB challenge. Additionally, RPMCs isolated from ACD rats with IL-37 intervention showed downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation, and reduction of β-hexosaminidase and histamine release under DNP-IgE/HSA treatment. Moreover, IL-37 treatment also significantly restrained NF-κB activation and P38 phosphorylation in ACD RPMCs. SIS3, a specific Smad3 inhibitor, abolished the suppressive effects of IL-37 on MC-mediated allergic inflammation, suggesting the participation of Smad3 in the anti-ACD effect of IL-37. These findings indicated that IL-37 protects against IL-33-regulated MC inflammatory responses via inhibition of NF-κB and P38 MAPK activation accompanying the regulation of Smad3 in rats with ACD. |
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Keywords: | Interleukin-37 Mast cells Allergic contact dermatitis Inflammation NF-κB P38MAPK IL-37" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" interleukin 37 MCs" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" mast cells RPMCs" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" rat peritoneal mast cells MAPK" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" mitogen-activated protein kinase NF-κB" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" nuclear factor κ-light-chain-enhancer of activated B cells Anti-DNP IgE" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" anti-dinitrophenyl immunoglobulin E DNP-HSA" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" dinitrophenyl-human serum albumin |
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