UVB and Proinflammatory Cytokines Synergistically Activate TNF-α Production in Keratinocytes through Enhanced Gene Transcription

Abstract

Ultraviolet B (UVB) irradiation potently induces cytokines in the skin, including interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α). The mechanism for TNF-α induction in UVB-irradiated keratinocytes is not clear. In the current study, we explored the effects of UVB and cytokines, alone or in combination in human keratinocytes. Keratinocytes were sham- or UVB-irradiated with 30 mJ/cm2, and then incubated in the absence or presence of IFN-α2b, TNF-α or IL-1α. UVB and IL-1α treatment synergistically enhanced TNF-α secretion and mRNA levels in human keratinocytes, similar to the findings reported previously in human fibroblasts. Exogenous recombinant TNF-α up-regulates its own mRNA level. However, addition of IFN-α2b did not show any additive effect on TNF-α mRNA induction. To understand the regulation of TNF-α mRNA by UVB, with or without IL-1α, we examined the transcription rate and half-life of TNF-α mRNA. Treatment of keratinocytes with IL-1α or UVB alone increased TNF-α gene transcription 4–5-fold over sham treatment, and TNF-α gene transcription increased 11-fold in cells treated with UVB plus IL-1α over sham. UVB with IL-1α did not enhance the half-life of TNF-α mRNA over that seen with UVB alone. In conclusion, TNF-α expression in primary keratinocytes is up-regulated transcriptionally by UVB and IL-1α.

Protective mechanism of morin against ultraviolet B-induced cellular senescence in human keratinocyte stem cells

“…Among the cytokines, TNF-α plays an important role in photodamage of epidermal cells. TNF-α release in response to UVB exposure induces nearby endothelial cells and keratinocytes to display cell adhesion molecules, thereby recruiting infl ammatory cells that secrete elastases and collagenases, leading to damage and aging of the skin (Strickland et al 1997, Rijken et al 2006, Bashir et al 2009). In this study, we found that the production of TNF-α , IL-1 β , and IL-6 was signifi cantly up-regulated in the UVBirradiated KSC when compared with the intact KSC.…”

Pathophysiology of Cutaneous Lupus Erythematosus

“…These cytokines subsequently mediate the release of secondary cytokines. This cytokine cascade, recruitment of immune cells, inflammation, and tissue destruction ultimately result in the photoinduced lesions of CLE [9,29].…”

“…KCs, as stated previously, are responsible for the production of IL-1 and TNF-α, primary cytokines in the inflammatory cascade. These primary cytokines have a wide array of effects, including activation of antigen-presenting cells, induction of adhesion molecules, and recruitment of immune cells [9,29].…”

Asian dust storm particles induce a broad toxicological transcriptional program in human epidermal keratinocytes

“…In addition, ADSPs had no significant effect on gene transcription of catalase, peroxiredoxins, superoxide dismutase, and NAD(P)H quinine dehydrogenase in HEK (Table 1). HEK produce pro-inflammatory cytokines and growth factors in response to various environmental stimuli (Bashir et al, 2009;Maeda et al, 2009). We evaluated whether ADSPs affected mRNA levels of cytokines known to be expressed in HEK such as IL-1␤, IL-6, IL-8, IL-18, interferon gamma (IFN␥), and granulocyte macrophage colony-stimulating factor (GM-CSF).…”