IL‐36γ has proinflammatory effects on human endothelial cells

Abstract

Interleukin-36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL-36 is now a recognised characteristic of psoriatic skin inflammation. IL-36 is known to induce inflammatory responses in dendritic cells, fibroblasts and epithelial cells. Although vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in skin inflammation, the effects of IL-36 on endothelial cells are unexplored. We here show that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated by IL-36γ stimulation, and this is reversed by the presence of the endogenous IL-36 receptor antagonist. IL-36γ-stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T-cells following IL-36γ stimulation of endothelial cells. These results suggest a role for IL-36γ in the dermal vascular compartment, and it is likely to enhance psoriatic skin inflammation by activating endothelial cells and promoting leucocyte recruitment.

Pathogenic role of exosomes and microRNAs in HPV‐mediated inflammation and cervical cancer: A review

“…Therefore, exosomes probably play an immunomodulatory role in the CC microenvironment. The pro‐inflammatory cytokine, IL‐36γ, has the ability to induce inflammation in keratinocytes via the Wingless/integrase 1 signaling pathway . Rana and colleagues demonstrated the presence of IL‐36γ inside exosomes derived from polyinosinic:polycytidylic acid (poly(I:C))‐treated keratinocytes.…”

“…The pro-inflammatory cytokine, IL-36γ, has the ability to induce inflammation in keratinocytes via the Wingless/integrase 1 signaling pathway. 136,137 Rana and colleagues demonstrated the presence of IL-36γ inside exosomes derived from polyinosinic:polycytidylic acid (poly(I:C))-treated keratinocytes. Previous studies have shown that HPV-16 inhibited the poly(I:C)-stimulated expression of some proinflammatory genes.…”

Increased expression of the interleukin‐36 cytokines in lesions of hidradenitis suppurativa

“…3,4 The IL-36 cytokines (IL-36a, IL-36b, IL-36c and IL-36RA) are interleukins of the IL-1 cytokine family and are mainly produced by keratinocytes. 5 The three different agonistic isoforms of IL-36 (IL-36a, IL-36b, IL-36c) are proinflammatory and are induced by themselves 6,7 as well as by other cytokines, such as IFN-c, IL-1a, IL-1b, IL-17, IL-22, IL-23 and TNFa. 5,[8][9][10] IL-36a, IL-36b and IL-36c have similar functions.…”

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

“…These cytokines are members of the wider IL‐36 family and are associated with the psoriatic skin inflammation . IL‐36 has inflammatory effects on a range of cells including stroma, T‐cells, fibroblast, and myeloid cells . The inflammatory effect of IL‐36 cytokines is blocked by the naturally occurring IL‐36 antagonist (IL‐36Ra) .…”

“…155 IL-36 has inflammatory effects on a range of cells including stroma, T-cells, fibroblast, and myeloid cells. 156,157 The inflammatory effect of IL-36 cytokines is blocked by the naturally occurring IL-36 antagonist (IL-36Ra). 156 The importance of IL-36 in psoriatic skin inflammation gained greater attention with the discovery that a loss of function in the IL-36Ra is associated with generalized pustular psoriasis (GPP) psoriasis (generalized pustular psoriasis).…”