| First Author | Chida D | Year | 2005 |
| Journal | Endocrinology | Volume | 146 |
| Issue | 12 | Pages | 5496-502 |
| PubMed ID | 16141396 | Mgi Jnum | J:129687 |
| Mgi Id | MGI:3769978 | Doi | 10.1210/en.2005-0409 |
| Citation | Chida D, et al. (2005) Involvement of corticotropin-releasing hormone- and interleukin (IL)-6-dependent proopiomelanocortin induction in the anterior pituitary during hypothalamic-pituitary-adrenal axis activation by IL-1alpha. Endocrinology 146(12):5496-502 |
| abstractText | IL-1alpha/beta and IL-6 are endogenous modulator of hypothalamo-pituitary-adrenal axis (HPAA) and are thought to play key roles in immune-neuroendocrine interactions during inflammation. Here, we show IL-1alpha induced a normal HPAA activation in IL-1alpha/beta knockout (KO) and IL-6 KO mice at 1 h; however, at 6 h HPAA activation was reduced relative to wild-type mice, indicating a role for endogenous IL-1alpha/beta and IL-6 in prolonged HPAA activation. We found that the induction of proopiomelanocortin (POMC) transcript in the anterior pituitary (AP) at 6 h in response to IL-1alpha was reduced in IL-1alpha/beta KO and IL-6 KO mice, as well as in CRH KO mice, suggesting IL-1alpha/beta, IL-6, and CRH are all required for POMC induction. The induction of CRH transcript in the paraventricular nucleus at 6 h and plasma IL-6 levels, in response to IL-1alpha, were reduced in IL-1alpha/beta KO mice. Because IL-1alpha-induced activation of signal transducer and activator of transcription 3 in the AP was also suppressed in IL-6 KO mice, we suggest that plasma IL-6 is first induced by IL-1alpha, and IL-6 activates signal transducer and activator of transcription 3 in the AP, leading to the induction of POMC in concert with CRH. Our results suggest a role for IL-1alpha/beta in the induction of POMC in the AP through the induction of two independent pathways, CRH and IL-6. |
