dinoprost and Dermatitis

Lipopolysaccharide (LPS) from Gram-negative bacteria has been reported to exert inflammatory reactions in epidermis, dermis, and sebaceous glands. Here, we demonstrated that the intradermal administration of Escherichia coli-derived LPS, three times a week for 4 weeks, to hamster auricle skin did not influence sebaceous morphology or sebum accumulation in sebaceous glands but in fact induced epidermal thickness. In addition, the administration of LPS, once a day for 2 days, augmented the production of cyclooxygenase 2 (COX-2) in sebaceous glands. Furthermore, LPS increased the production of prostaglandin F(2α) (PGF(2α) ) in hamster sebocytes. Moreover, the production of progelatinase A/promatrix metalloproteinase 2 (proMMP-2) was transcriptionally augmented by LPS and PGF(2α) in hamster sebocytes. Therefore, these results suggest that LPS directly increases inflammation by augmenting COX-2, PGF(2α) , and the PGF(2α) -mediated proMMP-2 production in sebaceous glands as well as epidermal inflammatory events in skin disorders including acne and folliculitis.

Topics: Animals; Cells, Cultured; Cricetinae; Cyclooxygenase 2; Dermatitis; Dinoprost; Ear Auricle; Epidermis; Gene Expression; Indomethacin; Lipopolysaccharides; Matrix Metalloproteinase 2; Sebaceous Glands; Sebum; Toll-Like Receptor 4

NC/Nga (NC) mice are known to develop dermatitis resembling atopic dermatitis (AD) in conventional (Conv) conditions, but not in specific pathogen-free (SPF) conditions. We reported that the ability of skin prostaglandin D(2) (PGD(2)) production, which might be the endogenous inhibitor of itching, was attenuated in skin-lesioned Conv-NC mice. We examined the age-related change in scratching, dermatitis symptoms, and skin PGs of SPF- and Conv-NC mice. In Conv-NC, PGD(2) increased at 7 weeks, at which scratching counts increased, but dermatitis did not develop. PGE(2), PGI(2) and PGF(2alpha) increased at 10 and 13 weeks, at which dermatitis developed. The ability to produce skin PGs was examined by measuring PGs after application of arachidonic acid or after mechanical scratching using a wire brush. In Conv-NC, PGD(2) production at 13 weeks was lower than at 7 weeks. In Conv-NC, hematopoietic PGD synthase (hPGDS) expression in the skin at 13 weeks was lower than at 7 weeks by Western blotting and immunohistochemical analysis. The increase of skin PGD(2) level in the early phase of the development of dermatitis is due to the stress of extensive scratching, but did not increase in spite of the stress of extensive scratching in the late phase, due to decreasing capacity of PGD(2) production attributable to decreasing hPGDS expression in Conv-NC mice. These results suggest that a decreased ability to produce skin PGD(2) production could enhance scratching and aggravate dermatitis in Conv-NC mice.

Topics: Animals; Arachidonic Acid; Blotting, Western; Dermatitis; Dinoprost; Dinoprostone; Epoprostenol; Immunohistochemistry; Intramolecular Oxidoreductases; Lipocalins; Male; Mice; Mice, Mutant Strains; Prostaglandin D2; Prostaglandins; Pruritus; Severity of Illness Index; Skin; Time Factors

1 In order to test the proposal that the anti-inflammatory effect of corticosteroids is attributable to inhibition of release of the prostaglandin precursor, arachidonic acid, the effect of systemic prednisolone on arachidonic acid and prostaglandin levels in abdominal skin of six patients receiving this treatment for alopecia totalis, was studied. 2 Inflammation was produced in an area of abdominal skin by topical application of 5% w/w tetrahydrofurfuryl nicotinate (THFN) cream. 3 The erythema produced was assessed visually, and exudate recovered from normal and inflamed skin, by a suction bulla technique. 4 Arachidonic acid and PGE2 and PGF2 alpha levels, as measured by gas chromatograph-mass spectrometry (GC-MS) were significantly elevated in the reddened (THFN) treated skin, compared with control areas. 5 After prednisolone treatment both arachidonic acid and prostaglandin levels in THFN-treated areas were suppressed near to values obtained from untreated skin, before prednisolone therapy. There was partial reduction of THFN induced erythema in three out of six subjects. Levels of arachidonic acid on control skin were not affected by the steroid. 6 These results provide direct evidence that steroids inhibit prostaglandin formation by blocking evoked rise in the concentration of free arachidonic acid. The relationship of this effect, in human skin, to the anti-inflammatory action of systemic steroids is uncertain.

Topics: Adolescent; Adult; Arachidonic Acids; Dermatitis; Dinoprost; Dinoprostone; Erythema; Furans; Humans; Male; Middle Aged; Nicotinic Acids; Prednisolone; Prostaglandins; Prostaglandins E; Prostaglandins F; Skin