Genetic deficiency or pharmacological inhibition of cyclooxygenase‐1 or ‐2 induces mouse keratinocyte differentiation in vitro and in vivo
| Autor: | Huei-Chen Lao, Robert Langenbach, Rachel M. Slade, Christopher A. Lee, Alisha R. Sessoms, Jacqueline K. Akunda |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Keratinocytes
Gene isoform Skin Neoplasms Antineoplastic Agents Apoptosis Biology medicine.disease_cause Biochemistry Mice In vivo Genetics medicine Animals Cyclooxygenase Inhibitors Protein Precursors Molecular Biology Cells Cultured Mice Knockout Sulfonamides Cyclooxygenase 2 Inhibitors integumentary system Epidermis (botany) Membrane Proteins Cell Differentiation Mouse Keratinocyte In vitro Isoenzymes Epidermal Cells Celecoxib Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Immunology Cyclooxygenase 1 biology.protein Cancer research Keratins Pyrazoles Cyclooxygenase Carcinogenesis Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 18:185-187 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Previously we demonstrated that genetic deficiency of the cyclooxygenases (COX-1 or COX-2) altered keratinocyte differentiation in mouse skin [Tiano et. al. (2002) Cancer Res. 62, 3395-3401]. In this study, we show that topical application of SC-560 (a COX-1 selective inhibitor) or celecoxib (COX-2 selective) to TPA-treated wild-type skin caused fivefold increases in the number of basal keratinocytes expressing the early differentiation marker keratin 1 (K1). In contrast to skin, COX-2 not COX-1 was the major isoform expressed in cultured primary keratinocytes. COX-1 was predominantly expressed in detached, differentiated cells, whereas COX-2 was found in the attached, proliferating cells. High Ca++ medium induced K1 and COX-1 in wild-type keratinocytes but did not change COX-2 expression. As observed in skin, COX-1-/- and COX-2-/- primary keratinocytes expressed fivefold more K1 than wild-type cells. K1 levels in cultured wild-type keratinocytes were also increased by treatment with celecoxib and indomethacin. However, unlike its in vivo effect, SC-560, possibly due to low COX-1 expression in cultured mouse keratinocytes, did not increase K1 levels. Furthermore, no increases in apoptotic cell numbers were observed in COX-deficient keratinocytes or COX-inhibitor treated wild-type cells. Thus, a major effect of COX inhibitors and COX-deficiency is the induction of keratinocyte differentiation. |
| Databáze: | OpenAIRE |
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