Dexamethasone Promotes Keratinocyte Proliferation by Triggering Keratinocyte Growth Factor in Mast Cells

Abstract

Background: The skin is a dynamic body organ that can be activated by both central and local hypothalamic-pituitary-adrenal axis systems. This phenomenon might be the crucial explanation why stress can cause relapse of chronic inflammatory skin diseases, such as psoriasis. Here, we determined the effects of mast cells on keratinocyte proliferation under stress hormone stimulation. Methods: We subcutaneously injected dexamethasone on the shaved back of mice and evaluated histological changes and keratinocyte growth factor (KGF) expression on dermal mast cells. Further, human mast cell line (HMC-1) and keratinocyte cell line (HaCaT) cells were treated with dexamethasone in vitro to observe the extent of proliferation and the expression of KGF. Finally, the supernatants of HMC-1 cells treated with dexamethasone were used for the culture of HaCaT cells to investigate the effect on proliferation. Results: We observed epidermal thickening in dexamethasone-injected mice, accompanied by an increase in the number of KGF-expressing dermal mast cells. Similar to mouse dermal mast cells, KGF was highly expressed in the human mast cell line HMC-1 following stimulation with dexamethasone. Further, dexamethasone-treated mast cells promoted keratinocyte proliferation in vitro. However, the effects of mast cells on keratinocytes were significantly diminished in the presence of anti-KGF-blocking antibodies. Conclusion: Taken together, our results show that a stressful environment may disturb skin barrier homeostasis through mast cell-derived KGF expression.

β-Ionone Attenuates Dexamethasone-Induced Suppression of Collagen and Hyaluronic Acid Synthesis in Human Dermal Fibroblasts

“…Circulating glucocorticoids can directly affect their peripheral target tissues, including in the skin. Thus, dexamethasone (a synthetic glucocorticoid) has been extensively used to mimic physiological stress in in vitro systems [ 36 , 37 , 38 ]. In clinical studies, it was reported that the serum level of cortisol in adult participants under severe psychological stress increases up to about 1 μM [ 39 , 40 , 41 ].…”

Quercetin protects human oral keratinocytes from lipopolysaccharide-induced injury by downregulating microRNA-22

“…Cyclin D1 interacts with cyclin-dependent kinases and increases phosphorylation of retinoblastoma protein to trigger proliferation, 14 while p16 and p53 can act as antiproliferative tumor suppressors. 15,16 In fact, the upregulation of p53 has been linked to OLP. 16 LPS significantly increased the rate of apoptosis in HOKs, which was associated with the upregulation of Bax and cleaved caspases 3 and 9.…”

“…15,16 In fact, the upregulation of p53 has been linked to OLP. 16 LPS significantly increased the rate of apoptosis in HOKs, which was associated with the upregulation of Bax and cleaved caspases 3 and 9. Quercetin significantly reversed all these effects of LPS.…”

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

“…On the other hand, MCs are reported to have both inhibitory and activating effects on KCs. For example, they can express keratinocyte growth factor (KGF) [ 58 ] and platelet-activating factor (PAF) [ 28 , 59 ] that activate KCs, while MC release of histamine, heparin and other MC mediators inhibits KC proliferation and, therefore, controls epidermal regeneration [ 60 , 61 ]. MC tryptase and chymase are reported to promote FB proliferation while inhibiting KC proliferation [ 62 ].…”