Browsing by Subject "IL-1ß"
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- PublicationOpen AccessP2X7 Receptor-Dependent Intestinal Afferent Hypersensitivity in a Mouse Model of Postinfectious Irritable Bowel Syndrome(Sociedad Americana de Inmunología, 2011) Keating, Christopher; Pelegrin, Pablo; Grundy, David; Martínez Cáceres, Carlos Manuel; Bioquímica y Biología Molecular B e InmunologíaThe ATP-gated P2X7 receptor (P2X7R) was shown to be an important mediator of inflammation and inflammatory pain through its regulation of IL-1 processing and release. Trichinella spiralis-infected mice develop a postinflammatory visceral hypersensitivity that is reminiscent of the clinical features associated with postinfectious irritable bowel syndrome. In this study, we used P2X7R knockout mice (P2X7R–/–) to investigate the role of P2X7R activation in the in vivo production of IL-1 and the development of postinflammatory visceral hypersensitivity in the T. spiralis-infected mouse. During acute nematode infection, IL-1–containing cells and P2X7R expression were increased in the jejunum of wild-type (WT) mice. Peritoneal and serum IL-1 levels were also increased, which was indicative of elevated IL-1 release. However, in the P2X7R–/– animals, we found that infection had no effect upon intracellular, plasma, or peritoneal IL-1 levels. Conversely, infection augmented peritoneal TNF- levels in both WT and P2X7R–/– animals. Infection was also associated with a P2X7R-dependent increase in extracellular peritoneal lactate dehydrogenase, and it triggered immunological changes in both strains. Jejunal afferent fiber mechanosensitivity was assessed in uninfected and postinfected WT and P2X7R–/– animals. Postinfected WT animals developed an augmented afferent fiber response to mechanical stimuli; however, this did not develop in postinfected P2X7R–/– animals. Therefore, our results demonstrated that P2X7Rs play a pivotal role in intestinal inflammation and are a trigger for the development of visceral hypersensitivity.
- PublicationOpen AccessTGF-ß1 and IL-6 expression in rat pineal gland is regulated by norepinephrine and interleukin-1 ß(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Tsai, S. Y.; Schluns, K. S.; Le, P. T.; McNulty, J. A.T he pineal g land is part of th e neur oendoc rin e system that modulat es immun e functions. Beca use the gland is outside the blood-brain barrier, il is accessibl e to dir ec t feedback from circul atin g cyto kin es that affec t th e sy nth esis and secreti on of melatonin . Recent studi es have suggested that intrinsic immunoregul atory cytokines med iate these neuro-immune int e ra cti o ns und er th e co ntr o l of sympathetic innervation to the pineal. This study focused on th e expression of transfo rmin g growt h factor-f3 1 (TGF-f3I) and interl eukin-6 (IL-6), two cy toki nes th at have important regula tory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-f3l, but not IL-6, was expressed in freshly dissected rat pineal glands from neo natal age (l -day-o ld) into ad ults. Immun ocy toc hemistry for TGF-B1 in adult glands revealed localization of this protein in astrocy telik e cells. The sy mp ath e tic ne ur o tr ansmitt e r norepinephrine (NE) increased transcript levels for both TGF-f31 and IL-6 in adu lt pinea l organ cultures. The effect of NE o n I L-6 exp ressio n was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregul atory molecule interleukin-l/3 (IL-l /3) up-regulat ed th e expression of both IL-6 and TGF-/31 in ad ult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF- /31 and IL-6 have intrinsic regul atory roles in the pinea l gland and that both neural and immune factors are important mechanisms of regulation.