Aging and Melanocytes Stimulating Cytokine Expressed by Keratinocyte and Fibroblast

Abstract

In the skin pigmentation, the actinic damage plays a major role (Leyden, Br J Dermatol 122:1–3, 1990), but the effect of chronologic cellular aging is also an important factor. The chief cellular components of the skin other than melanocytes are keratinocytes and fibroblasts, whose paracrine effects on melanocytes (rather than melanocyte itself) play an important role in the epidermal pigmentation (Yada et al., J Biol Chem 266:18352–18357, 1991; Imokawa et al., J Biol Chem 267:24675–24680, 1992; Imokawa et al., J Invest Dermatol 105:32–37, 1995; Imokawa et al., Biochem J 313:625–631, 1996; Grabbe et al., Arch Dermatol Res 161:78–84, 1994; Halaban et al., J Cell Biol 107:1611–1619, 1988; Puri et al., Arch Dermatol Res 288:633–635, 1996; Scott et al., J Invest Dermatol 96:318–322, 1991; Matsumoto et al., Biochem Biophys Res Commun 176:45–51, 1991; Imokawa G, Yada Y, Morisaki N, et al. Characterization of keratinocyte- and fibroblast-derived mitogens for human melanocytes – their roles in stimulated cutaneous pigmentation. Melanogenesis and malignant melanoma. In: Hori Y, Hearing VJ, Nakayama J (eds) Biochemistry, cell biology, molecular biology, pathophysiology, diagnosis and treatment. Elsevier, Amsterdam, pp 35–48, 1996). Human keratinocytes express several melanogenic cytokines, such as endothelin-1 (ET-1) (Yada et al., J Biol Chem 266:18352–18357, 1991; Imokawa et al., J Biol Chem 267:24675–24680, 1992; Imokawa et al., J Invest Dermatol 105:32–37, 1995), granulocyte macrophage colony-stimulating factor (GM-CSF) (Imokawa et al., Biochem J 313:625–631, 1996), stem cell factor (SCF), and basic fibroblast growth factor (bFGF) (Halaban et al., J Cell Biol 107:1611–1619, 1988; Puri et al., Arch Dermatol Res 288:633–635, 1996; Scott et al., J Invest Dermatol 96:318–322, 1991). Human fibroblasts, on the other hand, secrete several melanogenic cytokines such as bFGF, HGF, and SCF (Grabbe et al., Arch Dermatol Res 161:78–84, 1994; Matsumoto et al., Biochem Biophys Res Commun 176:45–51, 1991; Imokawa G, Yada Y, Morisaki N, et al. Characterization of keratinocyte- and fibroblast-derived mitogens for human melanocytes – their roles in stimulated cutaneous pigmentation. Melanogenesis and malignant melanoma. In: Hori Y, Hearing VJ, Nakayama J (eds) Biochemistry, cell biology, molecular biology, pathophysiology, diagnosis and treatment. Elsevier, Amsterdam, pp 35–48, 1996). Further, interleukin-1α (IL-1α), a pro-inflammatory cytokine, stimulates the production of ET-1 by keratinocytes and of HGF by fibroblasts (Imokawa et al., J Biol Chem 267:24675–24680, 1992; Matsumoto et al., Biochem Biophys Res Commun 188:235–243, 1992; Maas-Szabowski and Fusenig, J Invest Dermatol 107:849–855, 1996; Mildner et al., J Invest Dermatol 127:2637–2644, 2007). It has been reported that the overexpression of these melanogenic cytokines is responsible for the age-related pigmentary cutaneous disorders (Kadono et al., J Invest Dermatol 116:571–577, 2001; Hattori et al., J Invest Dermatol 122:1256–1265, 2004; Teraki et al., Br J Dermatol 135:918–923, 1996). The age-associated change was studied in cytokine secretion by keratinocytes and fibroblasts based upon this paracrine cytokine network within the skin for epidermal pigmentation mechanisms.