Effect of 12-O-tetradecanoylphorbol-13-acetate on inhibition of expression of keratin 1 mRNA in mouse keratinocytes mimicked by 12(S)-hydroxyeicosatetraenoic acid

Abstract

Differentiation of cultured keratinocytes is controlled by the calcium concentration of the medium and is marked by the expression of differentiation-specific keratins. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) alters the normal differentiation program and suppresses keratin (K) 1 expression. Based on reported similarities in the effects of TPA and the arachidonic acid metabolite 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), we hypothesized that 12(S)-HETE might suppress K1 expression in mouse keratinocytes. We also investigated the effect of pretreatment with 13(S)-hydroxyoctadecadienoic acid (13(S)-HODE) because others have reported that 13(S)-HODE prevents 12(S)-HETE-induced events. In our study, 100 nM 12(S)-HETE mimicked the effect of 500 nM TPA in suppressing K1 mRNA expression within 24 h of calcium-induced differentiation. Pretreatment with 100 nM 13(S)-HODE blocked the 12(S)-HETE effect but not the TPA effect. A role for protein kinase C (PKC) was suggested for both TPA and 12(S)-HETE based on the loss of response with the PKC inhibitors bryostatin-1 or RO-31-8220. Both TPA and 12(S)-HETE stimulated keratinocyte PKC activity. Pretreatment with 13(S)-HODE blocked the 12(S)-HETE-induced increase in PKC activity. Immunoblotting showed that whereas TPA caused a rapid, partial translocation of the PKC alpha isozyme, it had no effect on the distribution of PKC delta. Conversely, 12(S)-HETE had no effect on the distribution of PKC alpha but caused a complete translocation of PKC delta. Pretreatment with 13(S)-HODE prevented 12(S)-HETE-elicited translocation of PKC delta. We conclude that 12(S)-HETE mimics the effect of TPA on K1 mRNA and that the effect is mediated through different isoforms of PKC.

Three Constituents of Moringa oleifera Seeds Regulate Expression of Th17-Relevant Cytokines and Ameliorate TPA-Induced Psoriasis-Like Skin Lesions in Mice

“…These markers are needed to execute full cornification [20]. Treatment with TPA alters the normal differentiation program and suppresses keratin 1 expression, mimicking the incomplete cornification of psoriasis [21]. In our study, C2 and C3 increased the expression of both keratin 1 and loricrin, and decreased the expression of involcrin significantly, consistent with their more profound inhibitory effects on IL-17 and IL-23 expression (Figure 4C).…”

Eicosanoid Regulation of Angiogenesis in Human Prostate Carcinoma and Its Therapeutic Implications

“…A current report suggests that 12( S )‐HETE also stimulates activity of another phospholipase, PLD 35. Phospholipase products and an increase in cytosolic [Ca 2+ ] in turn promote membrane association of PKCα33 and PKCδ 38…”

“…35 Phospholipase products and an increase in cytosolic [Ca 2+ ] in turn promote membrane association of PKCα 33 and PKCδ. 38 In addition to its activation of the PKC pathway, 12(S)-HETE was shown to increase tyrosine phosphorylation of several proteins in focal adhesions, one of which was proven to be focal adhesion kinase (pp125FAK) and a 42/44-kDa doublet that migrated in the position of MAP kinase. 39 Subsequently, it was demonstrated that 12(S)-HETE can increase phosphorylation of MAP kinase 29 and activate it in part through PKCα and Raf (Szekeres and Honn, unpublished data).…”

12/15-Lipoxygenase deficiency reduces densities of mesenchymal stem cells in the dermis of wounded and unwounded skin

“…The p12‐LOX oxygenates AA to 12 S ‐HpETE and DHA to 14 S ‐HpDHA, and linoleic acid less efficiently to 13 S ‐HpODE . The p12‐LOX has no role in epidermal barrier function, but it may play a role in proliferation and differentiation of keratinocytes via its product 12 S ‐HETE . The e12 S ‐LOX expresses in the epidermis, hair follicles, and sebaceous glands .…”

“…54,55 The p12-LOX has no role in epidermal barrier function, 56 but it may play a role in proliferation and differentiation of keratinocytes via its product 12S-HETE. 57 The e12S-LOX expresses in the epidermis, hair follicles, and sebaceous glands. 58 It has a dual 12/15-LOX specificity with low reactivity (inactive on DHA); 55,59,60 its bioaction is unclear.…”