The release of pro‐inflammatory cytokines is mediated via mitogen‐activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes

Abstract

Toll-like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the 3-D structures of pathogen-associated molecules and are therefore useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides and monosodium urate (MSU) crystals in the activation of the TLR and NOD-like receptor (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NOD-like receptor P3 and TLR4, both of which are components of inflammasome complexes involved in the activation of interleukin (IL)-1β, were not expressed in keratinocytes. Transcriptomic analysis showed that the combination of MSU and lipopolysaccharide priming did not elicit significant results compared to MSU treatment, which induced the expression of TLR2, IL-6 and IL-8/chemokine (C-X-C motif) ligand 8 CXCL8 in the keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of extracellular signal-regulated kinase 1/2 and MAPK14/p38α mitogen-activated protein kinases. We concluded that MSU stimulates a pro-inflammatory response in keratinocytes via mitogen-activated protein kinase pathway to induce production of IL-8/CXCL8 chemokine (C-X-C motif) ligand 8 and TLR2.

Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage

“…Activation of Toll-like receptors (TLR) activates the nuclear factor-κB pathway resulting in the production of multiple pro-inflammatory cytokines including IL-6 and IL-8. This activation can be achieved through binding of LPS to TLR4 as well as binding of peptidoglycan to TLR2, two TLRs expressed by keratinocytes ( Pivarcsi et al., 2003 ; Ondet et al., 2017 ; Niebuhr et al., 2010 ). As C. acnes is a Gram-positive bacterium, activation of TLR2 by peptidoglycan is likely to occur ( Grange et al., 2009 ; Yuki et al., 2011 ).…”

Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor‐κB inflammatory signaling pathway in human skin cells

“…Keratinocytes contribute to the barrier functions of the epidermis through the formation of tight junctions and the stratum corneum and mediate inflammation through the secretion of cytokines, chemokines, and antibacterial peptides, and the expression of cellular adhesion molecules. 17,[36][37][38] Accordingly, we evaluated the inflammatory response of primary HEKs and human SCC cells to in vitro infection by C. t. bacteria. Cells treated with TNF, a typical inflammatory cytokine, served as a positive control for the induction of inflammatory genes.…”

TWEAK/Fn14 Activation Participates in Skin Inflammation

“…They secrete a broad spectrum of cytokines including proinflammatory cytokines, chemokines, and immunomodulatory cytokines and establish the local cytokine and chemokine milieu, which mediate multiple local and systemic consequences, such as migration of inflammatory cells, activation of immune responses, and proliferation and differentiation of keratinocytes and fibroblasts [ 48 – 50 ]. Keratinocytes can produce multiple cytokines such as IL-1, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and transforming growth factor- (TGF-) α [ 49 , 51 , 52 ]. Keratinocytes also synthesize the C-X-C chemokines, including interferon gamma-induced protein 10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and RANTES (regulated on activation, normal T cell expressed and secreted) [ 53 ].…”