IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation

Russell, Shane E.; Horan, Rachel M.; Stefańska, Anna; Carey, A.; Leon, Gemma; Aguilera, Mònica; Statovci, Donjete; Moran, Tara; Fallon, Padraic G.; Shanahan, Fergus; Brint, Elizabeth; Melgar, Silvia; Hussey, Séamus; Walsh, Patrick

doi:10.1038/mi.2015.134

Cited by 119 publications

(170 citation statements)

References 40 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…IL-36 α and IL-36 γ induce the expression of CXC chemokines on human intestinal epithelial cell line HT-29 cells in dose-dependent and time-dependent manners [89]. IL-36R −/− mice reduced the intestinal inflammation in DSS-induced acute colitis, associated with decreased innate inflammatory cell infiltration into the colon lamina propria [91]. Similarly, after infection with the enteropathogenic bacteria Citrobacter rodentium , IL-36R −/− mice reduced innate inflammatory cell infiltration and increased bacterial colonization in the colon, with enhanced Th17 and reduced Th1 responses [91].…”

Section: Il-1 Familymentioning

confidence: 99%

“…IL-36R −/− mice reduced the intestinal inflammation in DSS-induced acute colitis, associated with decreased innate inflammatory cell infiltration into the colon lamina propria [91]. Similarly, after infection with the enteropathogenic bacteria Citrobacter rodentium , IL-36R −/− mice reduced innate inflammatory cell infiltration and increased bacterial colonization in the colon, with enhanced Th17 and reduced Th1 responses [91]. Another group shows that IL-36 signaling may be important in the resolution of intestinal damage [92].…”

Section: Il-1 Familymentioning

confidence: 99%

See 1 more Smart Citation

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

Guan

Zhang

2017

Mediators of Inflammation

135

View full text Add to dashboard Cite

Cytokines play an important role in the immunopathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, where they drive and regulate multiple aspects of intestinal inflammation. The imbalance between proinflammatory and anti-inflammatory cytokines that occurs in IBD results in disease progression and tissue damage and limits the resolution of inflammation. Targeting cytokines have been novel strategies in the treatment of IBD. Recent studies show the beneficial effects of anticytokine treatments to IBD patients, and multiple novel cytokines are found to be involved in the pathogenesis of IBD. In this review, we will discuss the recent advances of novel biologics in clinics and clinical trials, and novel proinflammatory and anti-inflammatory cytokines found in IBD with focusing on IL-12 family and IL-1 family members as well as their relevance to the potential therapy of IBD.

show abstract

Section: Il-1 Familymentioning

confidence: 99%

Section: Il-1 Familymentioning

confidence: 99%

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

Guan

Zhang

2017

Mediators of Inflammation

135

View full text Add to dashboard Cite

show abstract

“…IL‐36 family cytokines (IL‐36α, IL‐36β and IL‐36γ), which belong to the IL‐1 super‐family, have recently emerged as key regulators of immune responses at mucosal sites . They are expressed by a range of cell types, including mucosal epithelial cells, macrophages and dendritic cells, and induced in response to TLR signaling .…”

Section: Introductionmentioning

confidence: 99%

“…They are expressed by a range of cell types, including mucosal epithelial cells, macrophages and dendritic cells, and induced in response to TLR signaling . IL‐36 cytokines are potent stimulators of the expression of neutrophil chemokines, such as IL‐8 and chemokine (C‐X‐C motif) ligand 1 ( CXCL1 ), by mucosal epithelial cells and innate immune cells, and accordingly are important regulators of neutrophil responses during infection . IL‐36 cytokines can also regulate immune responses by stimulating the expression of T‐cell chemokines, including CXCL10 and chemokine (C‐C motif) ligand 20 ( CCL20 ) .…”

Section: Introductionmentioning

confidence: 99%

“…EBI3 also has IL‐12 family cytokine‐independent functions, including mediating IL‐6 trans ‐signaling in CD4 + T cells, and inhibiting collagen expression in dermal fibroblasts . Significantly, IL‐36 cytokines can synergize with IL‐12 to promote the Th1 polarization of naïve T cells, and conversely inhibit the development of T regulatory cells …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MEK‐ERK signaling diametrically controls the stimulation of IL‐23p19 and EBI3 expression in epithelial cells by IL‐36γ

et al. 2018

View full text Add to dashboard Cite

Interleukin (IL)-36 cytokines are important regulators of mucosal homeostasis and inflammation. We previously established that oral epithelial cells strongly upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis. Here, we have established that IL-36γ stimulates the expression of the IL-12 cytokine family members, IL-23p19 and Epstein-Barr Virus-Induced Gene 3 (EBI3), by oral epithelial cells; their expression was also selectively stimulated by IL-36α. Notably, IL-23p19 and EBI3 expression was not stimulated by P. gingivalis, thus suggesting that their expression by the oral epithelium in response to P. gingivalis is likely to be mediated in an autocrine manner by IL-36γ. The IL-36γ-inducible expression of IL-23p19 and EBI3 was found to be diametrically regulated by the mitogen-activated protein kinase/extracellular signal regulated kinase (MEK)-extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, whereby the activation of MEK-ERK signaling likely functions as a negative feedback mechanism to limit EBI3 expression. Furthermore, epidermal growth factor receptor (EGFR) signaling, which is important for mucosal homeostasis, was demonstrated to modulate, in a MEK-ERK-dependent manner, the stimulation of IL-23p19 and EBI3 expression by IL-36γ. IL-23p19 and EBI3 have recently been shown to heterodimerize to form the novel cytokine IL-39 and promote neutrophil expansion. EBI3 has been shown to also have IL-12 cytokine family independent functions (e.g. mediating IL-6 trans-signaling). Thus, this study not only advances our understanding of how IL-36 cytokines may control mucosal inflammation, but also establishes EGFR signaling as a potentially important modulator of IL-36 cytokine function.

show abstract

Interleukin‐36α suppresses growth of non‐small cell lung cancer in vitro by reducing angiogenesis

Xie

et al. 2021

FEBS Open Bio

View full text Add to dashboard Cite

Interleukin-36α, a newly recognized IL-1 family member, has been previously reported to play a pivotal role in autoimmunity diseases and acute inflammatory reactions. Recently, several studies have indicated that IL-36α has potential anti-cancer effects against certain types of cancer. However, the expression pattern and functional role of IL-36α in non-small cell lung cancer (NSCLC) have not been elucidated. Here, we report that the mRNA and protein levels of IL-36α are significantly reduced in NSCLC tissues. Low levels of intratumoral IL-36α are correlated with higher tumor status, advanced TNM stage, increased vascular invasion, and shorter overall survival (OS). Intratumoral IL-36α expression is an independent prognostic factor for OS (hazard ratio = 3.081; P = 0.012) in NSCLC patients. Overexpression of IL-36α in lung cancer cells did not disturb cell proliferation, apoptosis, or cell cycle distribution in vitro, but markedly inhibited tumor growth in vivo. Mechanistically, IL-36α reduced the expression and secretion of vascular endothelial growth factor A (VEGFA) through inhibiting HIF-1α expression. Finally, decreased IL-36α expression was associated with high MVD and VEGFA in NSCLC patients. Together, our findings suggest that IL-36α expression is a valuable marker indicating poor prognosis in NSCLC patients.

show abstract

IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation

Cited by 119 publications

References 40 publications

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

MEK‐ERK signaling diametrically controls the stimulation of IL‐23p19 and EBI3 expression in epithelial cells by IL‐36γ

Interleukin‐36α suppresses growth of non‐small cell lung cancer in vitro by reducing angiogenesis

Contact Info

Product

Resources

About