Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice

Abstract

Although neuronal Toll-like receptors (TLRs) (e.g., TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive.Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone-ether-water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA (mRNA) expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, TNF-α, and IFN-γ were inhibited in TLR2 −/− mice, while CXCL2, IL-31, and IL-6 were inhibited in TLR7 −/− mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, and TNF-α were inhibited in TLR2 −/− mice, while CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, and TNF-α were inhibited in TLR7 −/− mice. Incubation with Staphylococcus aureus (S. aureus) peptidoglycan (PGN-SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142-3p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C-X-C Motif

Elevated expression of Toll-like receptor 7 and its correlation with clinical features in patients with primary Sjogren's syndrome

“…It was also shown that the level of IL-6 in the serum of pSS patients was much higher, which was proven to be positively connected with TLR7 expression. Keratinocytes stimulated the production of in ammatory molecules, including IL-6, in the psoriasis mouse model via TLR2 and TLR7 signaling pathways, leading to illness [25]. This corresponds to our discovery trend.…”

Sevoflurane Alters Serum Metabolites in Elders and Aging Mice and Increases Inflammation in Hippocampus

“…12 These results suggest that sevoflurane exposure promotes neuroinflammation. KEGG pathway analysis uncovered notable enrichment in starch and sucrose metabolism, carbohydrate digestion and absorption, IL-17 signaling pathway, TNF-α signaling pathway, and chemokine signaling pathway following sevoflurane treatment (Figure 1D), which is consistent with previous reports showing the secretion of inflammatory and oxidative stress mediators are associated with neurological diseases such as multiple sclerosis (MS), 15 chronic itch 16 and experimental autoimmune encephalomyelitis (EAE). 17,18 Microglial activation-mediated neuroinflammation plays an important role in neurodegenerative disease progression.…”

TLR4/7‐mediated host‐defense responses of gingival epithelial cells

“…For example, TLR7 mRNA and protein were clearly detected in primary human keratinocytes, which were further increased by induction of differentiation by calcium, 30 and both cultured human keratinocyte cells and mouse skin were reported to express TLR7 and respond to a TLR7 agonist. 31 Moreover, TLR7 protein expression was detected in normal human skin by immunostaining, which was further increased by IL-17. 32 Our current findings are consistent with these recent reports further supporting the role of TLR7 in human and mouse keratinocytes.…”

“…However, several more recent studies demonstrated TLR7 expression in keratinocytes. For example, TLR7 mRNA and protein were clearly detected in primary human keratinocytes, which were further increased by induction of differentiation by calcium, 30 and both cultured human keratinocyte cells and mouse skin were reported to express TLR7 and respond to a TLR7 agonist 31 . Moreover, TLR7 protein expression was detected in normal human skin by immunostaining, which was further increased by IL‐17 32 .…”