Interleukin 1 potentiates the secretion of beta-endorphin induced by secretagogues in a mouse pituitary cell line (AtT-20).

Abstract

Previous work has shown that corticotropin releasing factor, vasoactive intestinal peptide, phorbol ester, and forskolin cause the secretion of adrenocorticotropic hormone and ,3-endorphin from the AtT-20 mouse pituitary cell line. Human recombinant interleukin la and 1(3 also stimulated adrenocorticotropic hormone and (3-endorphin secretion from AtT-20 cells in a time-and dose-related manner. The effect appeared only after pretreatment with interleukin 1 (IL-I) for at least 18 hr and was maximum at 24 hr. After pretreatment of the cells over a period of time with IL-1, the secretion induced by corticotropin releasing factor and vasoactive intestinal peptide was increased in more than an additive manner. The enhancement of corticotropin releasing factorinduced (-endorphin release produced by IL-1 was apparent after 12 hr and reached a maximum at 24 hr. IL-1 did not affect forskolin-induced cAMP generation but enhanced the effect of forskolin on 3-endorphin secretion. This suggests that IL-1 does not induce adenylate cyclase and that forskolin causes the secretion of (3-endorphin by a mechanism independent of cAMP. IL-1 enhanced phorbol ester-induced (3-endorphin secretion. After prolonged treatment with phorbol ester (an activator ofprotein kinase C), the secretion induced by phorbol ester was abolished as well as the enhancement induced by IL-1. However, prolonged treatment with phorbol ester had no effect on IL-i-induced (3-endorphin secretion. These observations suggest that IL-i enhances peptide-generated secretion of (3-endorphin by inducing protein kinase C.Interleukin 1 (IL-1) is a polypeptide lymphokine (molecular mass of 17.5 kDa) produced by numerous cell types including macrophages, fibroblasts, and astrocytes (1). There are two distinct IL-1 genes expressing IL-1 activities, IL-la and IL-1p. Although IL-la and IL-1,B have less than 30% amino acid homology, they interact with the same receptors (2). IL-1 has a broad spectrum of biological activities as well as an important role in modulation of the immune responses and inflammation (3). It produces fever, somnolence, anorexia, and elevation of acute-phase proteins. It The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Interleukin 1 induces early protein phosphorylation and requires only a short exposure for late induced secretion of beta-endorphin in a mouse pituitary cell line.

“…1). These observations are in contrast to those obtained with TPA and TPA together with IL-1, where desensitization of PKC abolished the secretory effects of TPA as well as the potentiating effect on TPA-elicited secretion induced by pretreatment with IL-1 (1).…”

“…It has been recently demonstrated that human recombinant IL-1, after a long pretreatment (at least 18 hr), stimulates the release of f-endorphin in AtT-20 cells (1). Previous work in our laboratory has shown that prolonged pretreatment with IL-1 also potentiates the secretion induced by secretagogues such as corticotropin-releasing factor (CRF), vasoactive intestinal peptide, forskolin, norepinephrine, isoproterenol, and phorbol ester [phorbol 12- by IL-1 (1).…”

Evidence for arginine vasopressin as the primary activator of the HPA axis during adjuvant‐induced arthritis

“…In the presence of permissive levels of CRF, the increased expression of POMC mRNA and increased ACTH secretion is presumably due to the combined effect of high levels of AVP and the presence of locally produced (Stephanou et al, 1993) or circulating cytokines, which are likely to be elevated during chronic inflammation. In this regard it has been shown that prolonged exposure of AT-20 cells or rat cultured pituitary cells to interleukin-1 (IL-1) potentiates fl-endorphin responses to subsequent incubation with CRF (Fagarasan et al, 1989).…”

The immune system as the sixth sense

“…Another group was pretreated by first injecting ahCRF earlier observation [84]. Beginning with the original demonstration of IL-1-induced ACTH release from a corticotroph cell line [3], AtT20, and subsequent confirmations and demonstrations of this response with primary pituitary cell cultures [85][86][87][88][89][90], a controversy ensued as to whether in vivo IL-1-mediated ACTH increases originated at the level of the hypothalamus or pituitary gland [91]. Although the consensus of studies concluded that ACTH release occurs as a result of IL-1 eliciting hypothalamic CRH release and that the CRH is entirely responsible for pituitary ACTH secretion [92][93][94][95], these findings were difficult to reconcile with the abundance of IL-1 receptors in the pituitary gland when compared with the hypothalamus [96,97].…”