Differential modulation of transforming growth factor-beta by betamethasone-17- valerate and isotretinoin: corticosteroid decreases and isotretinoin increases the level of transforming growth factor-beta in suction blister fluid.
Retinoids and glucocorticoids are known to have a potential to modulate the expression of transforming growth factor-beta (TGF-beta). We investigated the effect of oral isotretinoin (13-cis-retinoic acid) on the expression of two distinct isoforms of TGF-beta, TGF-beta1 and TGF-beta2, in suction blister fluid and serum in acne patients. We also investigated the effect of topical glucocorticoid (betamethasone-17-valerate) and age on suction blister fluid TGF-beta1 in healthy volunteers. Six weeks of isotretinoin treatment caused a statistically significant 19% increase in suction blister fluid TGF-beta1. The suction blister fluid TGF-beta2 level remained below the sensitivity level of the immunoassay in many cases. Isotretinoin did not affect the serum TGF-beta1 or TGF-beta2 level. Betamethasone-17-valerate pretreatment for 3 days twice a day caused a statistically significant 17% decrease in suction blister fluid TGF-beta1. The active form of TGF-beta1 represented 5% of the total TGF-beta1 in suction blister fluid. Our diffusion calculations suggest that all TGF-beta1 and TGF-beta2 detected in suction blister fluid have diffused from systemic circulation. The increase in suction blister fluid TGF-beta1 after isotretinoin treatment seems to be of local origin, while the decrease in suction blister fluid TGF-beta1 after glucocorticoid pretreatment seems to be due to glucocorticoid-induced vasoconstriction resulting in decreased diffusion of TGF-beta1 from the circulation. Modulation of local interstitial fluid TGF-beta1 concentration may be one mechanism by which isotretinoin and glucocorticoids mediate their effects in skin.
Leivo
T
T
Department of Dermatology, University of Oulu and Oulu University Hospital, Oulu, Finland.
Arjomaa
P
P
Oivula
J
J
Vesterinen
M
M
Kiistala
U
U
Autio
P
P
Oikarinen
A
A
D000152:Acne Vulgaris / Q000188:drug therapy; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001624:Betamethasone Valerate / Q000494:pharmacology* / Q000627:therapeutic use; D001768:Blister / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D007641:Keratolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008233:Lymphotoxin-alpha / Q000097:blood / Q000378:metabolism*; D008297:Male
D000893:Anti-Inflammatory Agents; D007641:Keratolytic Agents; D008233:Lymphotoxin-alpha; D001624:Betamethasone Valerate; D015474:Isotretinoin