IL-17 contributes to the pathogenesis of obliterative bronchiolitis via regulation of M1 macrophages polarization in murine heterotopic trachea transplantation models

Meng, Qingshu; Liu, Jie; Lin, Fang‐Yue; Bao, Luer; Jiang, Yebin; Zheng, Li; Tie, Jinjun; Zhang, Lin; Liang, Xiaoting; Lu, Wei; Li, Yuan; Fan, Huimin; Zhou, Xiaohui

doi:10.1016/j.intimp.2017.08.022

“…It is well known that IL-17A is an important pro-inflammatory cytokine which prompts macrophages, T cells and epithelial cells to produce and release other chemokines or cytokines to mediate tissue infiltration, inflammation, destruction and remodeling [15, 16]. Thus, IL-17A exerts various functions, and has been implicated in several disease models [26–28].…”

Section: Discussionmentioning

confidence: 99%

“…As one of the most important pro-inflammatory cytokines, IL-17A has been found to be highly involved in several models of inflammatory or autoimmune diseases [13], such as colitis, asthma, multiple sclerosis, rheumatoid arthritis and renal allograft rejection. As one of the identified members of IL-17 family, IL-17A induces many other pro-inflammatory mediators such as IL-6, IL-23 by T cells [14], and stimulates the production of IL-1β and TNF-α by macrophages [15]. It mediates inflammation and immune response by recruiting neutrophils and regulating other inflammatory cells [16], propagating a broad immuno-inflammatory response.…”

Section: Backgroudmentioning

confidence: 99%

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Song

¹

,

Li

²

,

Xiao

³

et al. 2019

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Background The intestinal barrier integrity can be disrupted due to burn injury, which is responsible for local and systemic inflammatory responses. Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage. Interleukin-17A (IL-17A) plays a critical role in inflammatory diseases. However, the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood. In this study, we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury, and furthermore, we sought to determine the early source of IL-17A in the intestine. Methods Mouse burn model was successfully established with infliction of 30% total body surface area scald burn. The histopathological manifestation, intestinal permeability, zonula occludens-1 expression, pro-inflammatory cytokines were determined with or without IL-17A-neutralization. Flow cytometry was used to detect the major source of IL-17A+ cells in the intestine. Results Burn caused intestinal barrier damage, increase of intestinal permeability, alteration of zonula occludens-1 expressions, elevation of IL-17A, IL-6, IL-1β and tumor necrosis factor-α (TNF-α), whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption, maintained zonula occludens-1 expression, and noticeably, inhibited pro-inflammatory cytokines elevation. In addition, we observed that the proportion of intestinal IL-17A+Vγ4+ T subtype cells (but not IL-17A+Vγ1+ T subtype cells) were increased in burn group, and neutralization of IL-17A suppressed this increase. Conclusions The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines, and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined. Furthermore, Vγ4+ T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model. These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.

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“…qRT-PCR was applied for mRNA expression analysis [27]. PrimeScript RT Reagent Kits (TaKaRa, Japan) were used to reverse mRNA to cDNA.…”

Section: Methodsmentioning

confidence: 99%

Dynamic Profile of CD4⁺ T-Cell-Associated Cytokines/Chemokines following Murine Myocardial Infarction/Reperfusion

Yuan

¹

,

Tie

²

,

Xu

³

et al. 2019

Mediators of Inflammation

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CD4+ T-cells play crucial roles in the injured heart. However, the way in which different CD4+ T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4+ subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4+ T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1β, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1β, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1β, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-γ, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-γ, IL-12P70, IL-2, IL-18, TNF-α, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO-α were reduced, while IL-1β and MIP-2 were elevated at day 14. IL-13 and MIP-1β showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1β, MCP-3, and GRO-α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4+ T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.

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“…Macrophage infiltration had been turned out to be the main reason for rejection. The pathological damage degree of IL-17-/- mice was lighter than that of WT recipients in murine heterotopic tracheal transplantation models [ 12 ]. In another study, a highly reproducible preclinical model of OB, transplantation of minor histoincompatible lungs from C57BL/10 mice into C57BL/6 mice, was used.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-18: A Novel Participant in the Occurrence, Development, and Drug Therapy of Obliterative Bronchiolitis Postlung Transplantation

Shu

¹

,

Zhang

²

,

Zhang

³

et al. 2021

Disease Markers

0

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Background. Obliterative bronchiolitis (OB) was a main cause of deterioration of long-term prognosis in lung transplant recipients after the first posttransplant year. Proinflammatory cytokine interleukin-18 (IL-18) strengthened both the natural immunity and acquired immunity and played an important role in organ transplantation. The roles of IL-18 in the occurrence, development, and drug treatment of OB remained unclear. Methods. Small interfering RNA (siRNA) against mouse IL-18 (siRNA-IL-18) was used to silence IL-18 expression. Mouse heterotopic tracheal transplantation model was used to simulate OB. Recipient mice were divided into 5 groups ( n = 12 ) according to donor mouse strains and drug treatment: isograft group, allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group. The luminal obliteration rates were pathological evaluation. Expressions of cytokines and MMPs were detected by real-time PCR, western blot, and enzyme chain immunosorbent assay (ELISA). Results. The luminal obliteration rates of IL-18 of the siRNA-IL-18 group were significantly lower than those of the negative control group ( p < 0.0001 ) and the blank control group ( p = 0.0002 ). mRNA expressions of IFN-γ, EMMPRIN, MMP-8, and MMP-9 of the siRNA-IL-18 group were significantly lower than those of the negative and blank control groups. No tracheal occlusion occurred in grafts of the isograft group. The rates of tracheal occlusion of the allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group were 72.17 ± 4.66 %, 40.33 ± 3.00 %, 38.50 ± 2.08 %, and 23.33 ± 3.24 %, respectively. There were significant differences between the 4 groups ( p < 0.001 ). Serum protein expressions of IL-17 ( p = 0.0017 ), IL-18 ( p = 0.0036 ), IFN-γ ( p = 0.0102 ), and MMP-9 ( p = 0.0194 ) were significantly decreased in the allograft+tacrolimus+azithromycin group compared to the allograft group. Conclusions. IL-18 could be a novel molecular involved in the occurrence, development, and drug treatment of OB.

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IL-17 contributes to the pathogenesis of obliterative bronchiolitis via regulation of M1 macrophages polarization in murine heterotopic trachea transplantation models

Cited by 14 publications

References 45 publications

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Dynamic Profile of CD4⁺ T-Cell-Associated Cytokines/Chemokines following Murine Myocardial Infarction/Reperfusion

Interleukin-18: A Novel Participant in the Occurrence, Development, and Drug Therapy of Obliterative Bronchiolitis Postlung Transplantation

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IL-17 contributes to the pathogenesis of obliterative bronchiolitis via regulation of M1 macrophages polarization in murine heterotopic trachea transplantation models

Cited by 14 publications

References 45 publications

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Dynamic Profile of CD4+ T-Cell-Associated Cytokines/Chemokines following Murine Myocardial Infarction/Reperfusion

Interleukin-18: A Novel Participant in the Occurrence, Development, and Drug Therapy of Obliterative Bronchiolitis Postlung Transplantation

Contact Info

Product

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About

Dynamic Profile of CD4⁺ T-Cell-Associated Cytokines/Chemokines following Murine Myocardial Infarction/Reperfusion