Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation.

Abstract

Interleukin 1 (IL-1) is a family of polypeptides initially found to be produced by activated monocytes and macrophages that mediate a wide variety of cellular responses to injury and infection. Epidermal epithelial cells (keratinocytes) produce "epidermal cell-derived thymocyte activating factor" or ETAF, which has been recently shown to be identical to IL-1. Human epidermis is normally exposed to significant amounts of solar ultraviolet radiation. Certain ultraviolet wavelengths (UVB, 290-320 nm) are thought to be responsible for most of the immediate and long-term pathological consequences of excessive exposure to sunlight. In this study, we asked whether exposure to UVB irradiation induced IL-1 gene expression in cultured human keratinocytes. Cultured human keratinocytes contain detectable amounts of IL-i a and ft mRNA and protein in the absence of apparent stimulation; these levels could be significantly enhanced 6 h after exposure to 10 ng/ml of 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Exposure to UVB irradiation with an emission spectrum comparable to that of sunlight (as opposed to that of an unfiltered artificial UV light source) significantly increased the steady state levels IL-la and , mRNA in identical populations of human keratinocytes. This was reflected in the production of increased IL-i activity by these cultures in vitro. In the same cell population, exposures to UVB irradiation did not alter the level of actin mRNA; therefore, the effect of UV irradiation on IL-1 represents a specific enhancement of IL-1 gene expression. Local increases of IL-1 may mediate the inflammation and vasodilation characteristic of acute UVB inured skin, and systemic release ofthis epidermal IL-1 may account for fever, leukocytosis, and the acute phase response seen after excessive sun exposure.

Modulation of ultraviolet‐induced hyperalgesia and cytokine upregulation by interleukins 10 and 13

“…Increased levels of proin¯ammatory and antiin¯am-matory cytokines in the skin or in the plasma have also been observed following UVR. As illustration, increases in proin¯ammatory cytokines such as IL-1b (Araneo et al, 1989;Gahring et al, 1984;Kupper et al, 1987;Oxholm et al, 1988), TNF-a (KoÈ ck et al, 1990;Oxholm et al, 1988;Streilein et al, 1994) and in antiin¯ammatory cytokines, mainly IL-4 and IL-10 (Araneo et al, 1989;Rivas & Ullrich, 1992;Shreedhar et al, 1998) were reported. Thus our observation, of increased levels of IL-1b and TNF-a, correlates well with previous reports and are in line with established role of these mediators in in¯ammatory reactions.…”

“…Skin in¯ammation due to acute exposure to UVR has been shown to be characterized by the release of neuropeptides, histamine, prostaglandins, serotonin and oxygen radicals (Benrath et al, 1995;Eschenfelder et al, 1995;Greaves & Sùndergaard, 1970;Hawk et al, 1983;Hruza & Pentland, 1993) and the upregulation of proin¯ammatory cytokines, such as interleukin (IL)-1 (Araneo et al, 1989;Gahring et al, 1984;Kupper et al 1987) and IL-6 and tumour necrosis factor alpha (TNF-a) (KoÈ ck et al, 1990;Oxholm et al, 1988). Prolonged or repetitive exposure to UVB, however, has been reported to lead to generalized immunosuppression (Streilein et al, 1994) through the production/secretion of antiin¯ammatory cytokines such as IL-4, and IL-10 (Araneo et al, 1989;Rivas & Ullrich, 1992;Shreedhar et al, 1998).…”

Identification of macrophage migration inhibitory factor (MIF) in human skin and its immunohistochemical localization

“…Cytokines released from keratinocytes can be induced by environmental stimuli such as trauma, bacterial toxins and ultraviolet light. For example, IL-1 and TNF-ct release from keratinocytes are induced by ultraviolet radiation [11,12], and physical damage to keratinocytes can stimulate IL-1 release [13]. In addition, IL-1 in concert with other cytokines such as GM-CSF, IL-6, and TGF-t~, stimulates keratinocyte proliferation [14,15].…”

The pathophysiology of photosensitivity in lupus erythematosus

“…UVB also induces IL-1a gene transcription in keratinocytes (207) and elevates circulating levels of IL-1a bioactivity (208). Like TNF-a, IL-1 has broad pro-inflammatory activities (209).…”