Altered expression of CCN1 in oral lichen planus associated with keratinocyte activation and IL‐1β, ICAM1, and CCL5 up‐regulation

Abstract

Background: Emerging evidence indicates that CCN1 is a novel inflammation-regulated mediator involved in the pathogenesis of some immune-mediated inflammatory diseases. The objective of this study was to investigate the preliminary roles of CCN1 and its related cytokines IL-1β, CCL5, and ICAM1 in oral lichen planus (OLP). Methods: CCN1 expression levels in biopsies from OLP patients against normal oral mucosa (NOM) using immunohistochemistry (42 OLP vs 9 NOM) and RT-qPCR (20 OLP vs 20 NOM) were compared, respectively. The correlation of CCN1 and IL-1β, CCL5, and ICAM1 expression was examined by RT-qPCR in tissue samples and an in vitro cell culture system using keratinocyte HaCaT cells incubated with lipopolysaccharides. Results: Immunohistochemistry showed that CCN1 protein mainly expressed in the cytoplasm of epithelial keratinocytes of OLP. Consistently, RT-qPCR revealed that mRNA expression of CCN1 was increased in OLP compared with NOM (P < .05) and positively correlated with the high expression of IL-1β, ICAM1, and CCL5 (P < .001), respectively. Importantly, an in vitro study showed that keratinocyte proliferation significantly (P < .05) increased by CCN1 stimulation. Moreover, IL-1β, ICAM1, and CCL5 expression in keratinocytes stimulated by CCN1 was increased (P < .05), respectively. Conclusions: This preliminary study for the first time reported that altered expression of CCN1 was associated with high expression of IL-1β, ICAM1, and CCL5 in OLP. And we demonstrated CCN1 promoted keratinocyte activation, as well as IL-1β, ICAM1, and CCL5 production in keratinocytes. Our data indicated that the potential role of CCN1 and its related cytokines was involved in the pathogenesis of OLP.

CCL5/CCR5 axis in human diseases and related treatments

“…In addition, Th1 cells secret IFN- to increase CCL5 expression and aggravate epithelium damage. 63 , 64 On the other hand, OLP-related mast cell degranulation could cause upregulation of the cytokines mediating the expression of CCL5, such as TNF- . As a result, the increased CCL5 would strengthen the accumulation of specific T cells, which further prolongs the inflammatory response.…”

Epigallocatechin‐3‐gallate exhibits anti‐inflammatory effects in a human interface dermatitis model—implications for therapy

“…Amongst them is CD54, also known as ICAM1, which is known to be overexpressed in diseases featuring ID. [82][83][84][85] Its experimental blockade results in strongly decreased capacity of keratinocytes to activate co-cultured naive T cells via disruption of cell-cell contact formation 81 suggesting ICAM1 as a potential therapeutic target in inflammatory skin disorders. Interestingly, EGCG strongly downregulates ICAM1 expression in ID-like stimulated keratinocytes in our approach.…”

Chemopreventive efficacy of salvianolic acid B phospholipid complex loaded nanoparticles against experimental oral carcinogenesis: implication of sustained drug release

“…All slides were stained using previously optimized conditions with appropriate positive and negative controls. The quantitative evaluation of immunoreactivity was performed according to the criteria of staining intensities described previously (20). Briefly, 5 digital images of highpower fields at 400× magnification selected randomly on immunostained sections were captured by the DP 70 CCD camera (Olympus, Tokyo, Japan).…”

“…To evaluate the implication of sustained drug release after withdrawal (weeks [19][20][21][22] of nano-SAB on cell proliferation and cell cycle markers, we focused on the differences in the expression patterns of these markers at week 18 versus week 22 (Figure 4). The expression levels of Ki-67, PCNA, and cyclin D1 in groups A and B were significantly higher at week 22 than week 18 (all P<0.05, t-test).…”