Transcriptional regulation of interleukin-6 in pituitary folliculo-stellate TtT/GF cells.
Interleukin-6 (IL-6) secreted by pituitary folliculo stellate (FS) cells plays an important role in the control of pituitary function and proliferation. We demonstrate that in FS TtT/GF cells, estradiol (E(2)) inhibits dose dependently pituitary adenylate cyclase activating polypeptide (PACAP)-stimulated IL-6 secretion and transcription. We studied transcription factors involved in IL-6 stimulation by PACAP. Point mutations in kappaB, TRE, NF-IL-6 and CRE sites in the IL-6 promoter show that PACAP stimulates IL-6 through TRE and CRE sites. Accordingly, PACAP stimulated AP-1 and CREB transcriptional activity and E(2) inhibited TRE-LUC but not CRE-LUC activation. Thus, we demonstrate that transcription factors of the CREB and AP-1 family are critical for the stimulation of IL-6 by PACAP in TtT/GF cells and that estrogens block this stimulation by inhibiting AP-1 activity. The regulatory elements involved in IL-6 transcription in TtT/GF FS cells contribute to understand the specificity of the anterior pituitary gland paracrine pathways.
Nagashima
Alberto Carbia
AC
Laboratorio de Fisiología y Biología Molecular, Departmento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, PabellónII, Argentina.
Giacomini
Damiana
D
Castro
Carolina Perez
CP
Pereda
Marcelo Paez
MP
Renner
Ulrich
U
Stalla
Günter K
GK
Arzt
Eduardo
E
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic
C495402:Adcyap1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D015850:Interleukin-6; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018808:Transcription Factor AP-1; D004958:Estradiol; D000242:Cyclic AMP