Nicotine and Biochanin A, but Not Cigarette Smoke, Induce Anti-Inflammatory Effects on Keratinocytes and Endothelial Cells in Patients with Behçet's Disease

Abstract

During periods of smoking, patients with Behçet's disease have less oral aphthae than in abstinence. To elucidate this observation, human keratinocytes and dermal microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients with Behçet's disease and 20 healthy controls for 4 hours. Maximum non-toxic concentrations were determined and the cells were further treated with 6 microM nicotine, 3.3% cigarette smoke extract (CES), 100 microM biochanin A, and 6.25/12.5 microM pyrrolidine dithiocarbamate alone and in combinations for 24 hours. Serum IL-8 levels of patients were significantly lower than those of controls. However, after 4 hours incubation with patients' sera, IL-8 release by both cell types was markedly increased when compared with the corresponding serum levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release were after 4 hours similar with the corresponding levels in serum. IL-1 was not detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1 maintained in both patients' and controls' sera, but only IL-6 release by keratinocytes maintained in patients' sera. VEGF release by both cells was markedly increased after nicotine treatment in either serum. CES significantly decreased IL-8 release and increased production of VEGF in keratinocytes maintained in patients' serum. The phytoestrogen biochanin A alone and in combination with nicotine further decreased the secretion of IL-8, -6, and VEGF in all experimental settings. Our data support a specific anti-inflammatory effect of nicotine on keratinocytes and endothelial cells maintained in the serum of patients with Behçet's disease. Moreover, biochanin A is likely to exhibit similar and even more profound results than nicotine.

Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation

“…That nicotine can influence keratinocytes and other epithelial cells is well documented. In patients with oral ulcerations such as Behcets disease the use of nicotine appears to be anti-inflammatory since patients with this disease have less oral apthae during periods of smoking (Kalayciyan et al, 2007;Soy et al, 2000). Of note is that the skin is not the only tissue where ulcerative disease is associated with the overproduction of inflammatory cytokines such as TNFα, and whose progression is altered by nicotine.…”

“…Further, UVR exposure is a common and wellcharacterized method of inducing inflammation in the skin, and we have employed this method for many years to study this effect Gahring et al, 1984). Keratinocyte expression of nAChR has been demonstrated to have important roles in keratinocyte adhesion and motility (Chernyavsky et al, 2004;Grando et al, 1995;Zia et al, 1997), differentiation (Arredondo et al, 2002;Grando et al, 1996), apoptosis (Arredondo et al, 2003;Nguyen et al, 2001), and certain components of inflammation (Kalayciyan et al, 2007;Kurzen et al, 2007).…”

Nicotine Alters Morphology and Function of Retinal Pigment Epithelial Cells in Mice

“…IL8 has been proposed to be one of the main cytokines secreted by RPE cells during their response to foreign challenge stresses like proinflammatory/cytokine treatment (Bian et al 1996;Ebihara et al 2007;Elner et al 1990;Fukuoka et al 2003) or injury (Yoshida et al 2001). In some cases, nicotine was reported to inhibit IL8 production in various cells (Kalayciyan et al 2007;Louvet et al 1999;Sugano et al 1998;Patton et al 2006), but in other cases, nicotine was reported to increase IL8 production (Iho et al 2003;Wendell and Stein 2001). In this study, although cultured RPE cells spontaneously secreted certain a amount of IL8 and LPS dramatically enhanced IL8 production, up to 2 mM of nicotine in RPE culture failed to affect IL8 production, either at the mRNA level ( Figure 5A) or the protein level ( Figure 5B).…”

Occluded Cigarette Smoke Exposure Causing Localized Chloracne-Like Comedones

“…Although a number of studies have examined well-known constituents of cigarette smoke such as nicotine - which has some dermatological anti-inflammatory properties as well as a capacity for stimulating epidermal and mucosal keratinocyte differentiation - the specific effects of the vast majority of the many chemical components of cigarette smoke remain uncharacterized [9,10]. While the literature contains mixed data concerning the systemic effect of smoking and its association with acne vulgaris, Capitanio et al [11] reported a strict correlation with cigarette smoking and the development of comedonal postadolescent acne, a predominantly noninflammatory form of acne characterized by retentional comedones [1,11,12,13].…”