Leptin regulates the pro-inflammatory response in human epidermal keratinocytes

Abstract

The role of leptin in cutaneous wound healing process has been suggested in genetically obese mouse studies. However, the molecular and cellular effects of leptin on human epidermal keratinocytes are still unclear. In this study, the whole-genome-scale microarray analysis was performed to elucidate the effect of leptin on epidermal keratinocyte functions. In the leptin-treated normal human keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro-inflammatory responses, extracellular matrix organization, and angiogenesis. Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7, which play roles in which is important in the regulation of cutaneous inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly-associated centromere protein A (CENPA) and CENPM was confirmed in the leptin-treated NHKs. However, the expression of CENPA and CENPM was not coupled with those of other chromosome passenger complex like Aurora A kinase, INCENP, and survivin. In cell growth kinetics analysis, leptin had no significant effect on the cell growth curves of NHKs in the normal growth factor-enriched condition. Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be directly associated with mitotic regulation during inflammation.

Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light‐breed horses

“…The lack of significant lamellar inflammatory cell infiltrates accompanying this model suggests that the source of pro‐inflammatory cytokines and chemokines detected within lamellar tissue is likely to be the major cell type in this tissue, the lamellar keratinocyte. Both human and equine keratinocytes produce pro‐inflammatory cytokines and chemokines when stimulated with various pathogen‐associated molecular pattern molecules in vitro, and these cells likely have the capacity to elaborate these substances in vivo in response to various stimuli as well (including exposure to elevated leptin concentrations). Although evaluating mRNA concentrations alone is useful to identify the activation of inflammatory signaling pathways in general, determining the role of the individual cytokines/chemokines involved would necessitate quantification of the native peptides/proteins as well in some way (immunoblotting, IF, flow cytometry, etc.…”

<p>Identification of Aurora Kinase A as a Biomarker for Prognosis in Obesity Patients with Early Breast Cancer</p>

“…The molecular mechanisms that link obesity breast cancer are complex, the main mechanisms which can explain this link are leptin, adipose chronic inflammation, sex hormone alternation, and insulin signaling. 4,[24][25][26] Kim et al 27 demonstrated Aurora A-related cell cyclin with a spatially localized response to IGF-1 using high throughput single-cell imaging to confirm the hypothesis that the presence of various cellular sub-populations interact with IGF-1. Previous studies highlighted that high Aurora A expression was strongly associated with worse survival of breast cancer and as an independent prognostic marker.…”

The role of leptin in selected skin diseases

“…However, by activation of the STAT3 signaling pathway, leptin can trigger proliferation, differentiation, migration, and stabilization of cells in the skin as well as it may modulate angiogenesis [28,29]. Lee et al investigated the molecular mechanism of leptin impact on keratinocytes by observation genomewide transcriptional responses of normal human keratinocytes (NHKs) [25] Leptin enhanced intracellular signaling and induced pro-inflammatory reaction in keratinocytes, by increasing the production of interleukins in a similar mechanism as it is observed in immune cells. Above mentioned leptin action might have a significant impact on the pathomechanism of skin diseases connected with obesity [25][26][27][28][29][30][31].…”

“…Lee et al investigated the molecular mechanism of leptin impact on keratinocytes by observation genomewide transcriptional responses of normal human keratinocytes (NHKs) [25] Leptin enhanced intracellular signaling and induced pro-inflammatory reaction in keratinocytes, by increasing the production of interleukins in a similar mechanism as it is observed in immune cells. Above mentioned leptin action might have a significant impact on the pathomechanism of skin diseases connected with obesity [25][26][27][28][29][30][31]. With a high probability, leptin derived centrally as well as in paracrine or even autocrine way can affect the skin under both physiological and pathological conditions.…”