Role of tumor necrosis factor receptors in an animal model of acute colitis

Rojas‐Cartagena, Carmencita; Flores, Idhaliz; Appleyard, Caroline B.

doi:10.1016/j.cyto.2005.08.001

Cited by 48 publications

(37 citation statements)

References 48 publications

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“…In contrast, blocking of central TNF␣ signaling alone was effective. Because TNF␣ is implicated in local inflammatory damage in the colon after TNBS (55,56), and the CNS can affect colonic inflammation (57), we also verified that the reversal of the reduced PTZ seizure threshold was not due to a reduction in the peripheral inflammatory response.…”

Section: Discussionsupporting

confidence: 48%

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Riazi

Galic²,

Kuzmiski³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

354

307

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Peripheral inflammation leads to a number of centrally mediated physiological and behavioral changes. The underlying mechanisms and the signaling pathways involved in these phenomena are not yet well understood. We hypothesized that peripheral inflammation leads to increased neuronal excitability arising from a CNS immune response. We induced inflammation in the gut by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to adult male rats. To examine the excitability of the brain in vivo, we administered pentylenetetrazole (PTZ; a GABAergic antagonist) intravenously to evoke clonic seizures. Rats treated with TNBS showed increased susceptibility to PTZ seizures that was strongly correlated with the severity and progression of intestinal inflammation. In vitro hippocampal slices from inflamed, TNBS-treated rats showed increased spontaneous interictal burst firing following application of 4-aminopyridine, indicating increased intrinsic excitability. The TNBS-treated rats exhibited a marked, reversible inflammatory response within the hippocampus, characterized by microglial activation and increases in tumor necrosis factor ␣ (TNF␣) levels. Central antagonism of TNF␣ using a monoclonal antibody or inhibition of microglial activation by i.c.v. injection of minocycline prevented the increase in seizure susceptibility. Moreover, i.c.v. infusion of TNF␣ in untreated rats for 4 days also increased seizure susceptibility and thus mimicked the changes in seizure threshold observed with intestinal inflammation. Our finding of a microglia-dependent TNF␣-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological and behavioral changes associated with chronic inflammation.4-aminopyridine ͉ cytokine ͉ pentylenetetrazole ͉ seizure ͉ colitis

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Section: Discussionsupporting

confidence: 48%

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Riazi

Galic²,

Kuzmiski³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

354

307

View full text Add to dashboard Cite

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“…IFN-␥, a well-known type 1 helper T (Th1) cytokine, was chosen on the basis of studies showing that UC and TNBS-colitis in animals are associated with a cell-mediated immune response involving the activation of Th1 lymphocytes and subsequent secretion of IFN-␥ (3,33). IFN-␥ levels are elevated in UC and TNBS-colitis (23,33); additionally, TNF-␣ as well as mRNA for TNF receptors (TNF-RI and TNF-RII) are significantly increased in the colon of experimental animals (29). Furthermore, TNF-␣ is the target for the drug infliximab, which is used in inflammatory bowel disease (IBD) treatment (34).…”

mentioning

confidence: 99%

IFN-γ and TNF-α decrease serotonin transporter function and expression in Caco2 cells

Foley¹,

Pantano²,

Ciolino³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Foley KF, Pantano C, Ciolino A, Mawe GM. IFN-␥ and TNF-␣ decrease serotonin transporter function and expression in Caco2 cells. Am J Physiol Gastrointest Liver Physiol 292: G779 -G784, 2007. First published December 14, 2006; doi:10.1152/ajpgi.00470.2006.-Recent studies have shown that mucosal serotonin (5-HT) transporter (SERT) expression is decreased in animal models of colitis, as well as in the colonic mucosa of humans with ulcerative colitis and irritable bowel syndrome. Altered SERT function or expression may underlie the altered motility, secretion, and sensation seen in these inflammatory gut disorders. In an effort to elucidate possible mediators of SERT downregulation, we treated cultured colonic epithelial cells (Caco2) with conditioned medium from activated human lymphocytes. Application of the conditioned medium caused a decrease in fluoxetine-sensitive [3 H]5-HT uptake. Individual proinflammatory agents were then tested for their ability to affect uptake. Cells were treated for 48 or 72 h with PGE2 (10 M), IFN-␥ (500 ng/ml), TNF-␣ (50 ng/ml), IL-12 (50 ng/ml), or the nitric oxide-releasing agent S-nitrosoglutathione (GSNO; 100 M).[ 3 H]5-HT uptake was then measured. Neither PGE nor IL-12 had any effect on [ 3 H]5-HT uptake, and GSNO increased uptake. However, after 3-day incubation, both TNF-␣ and IFN-␥ elicited significant decreases in SERT function. Neither TNF-␣ nor IFN-␥ were cytotoxic when used for this period of time and at these concentrations. These two cytokines also induced decreases in SERT mRNA and protein levels. By altering SERT expression, TNF-␣ and IFN-␥ could contribute to the altered motility and expression seen in vivo in ulcerative colitis or irritable bowel syndrome.SERT; tumor necrosis factor; interferon; colitis; inflammatory bowel disease; inflammation SEROTONIN (5-hydroxytryptamine; 5-HT) is the main monoamine signaling molecule in the gut, where it acts as a paracrine neurotransmitter (9, 25). Specialized enteroendocrine cells, enterochromaffin cells, release 5-HT into the lamina propria of the intestines, where it activates receptors located on processes of intrinsic and extrinsic primary afferent neurons. This leads to activation of local motor and secretory reflexes and the transduction of sensory signals to the brain stem and spinal cord. A critical aspect of paracrine and neurotransmitter signaling is the termination of transmission by degradation or removal of the signaling molecule. In the case of 5-HT, this involves rapid clearance of 5-HT from the intercellular space by the 5-HT reuptake transporter (SERT), which is expressed by mucosal epithelial cells (7,21,36).SERT is a member of the highly conserved Na ϩ /Cl Ϫ -dependent transporter gene family containing 12 transmembrane domains (2). Transporters for 5-HT and other monoamines are of particular interest because they are sites of action for most clinically efficacious antidepressants, as well as for psychoactive drugs of abuse such as amphetamines, cocaine, and MDMA (ecstasy). Furthermore, abnormal expression o...

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“…Higher levels of circulating ICAM-1 and E-selectin have been reported in CD [20]. Furthermore, ICAM-1 expression is upregulated in intestinal mucosa of inflammatory bowel disease [23]. Therefore, these codon substitutions might confer an alteration in selectin-ligand binding specificities and affect kinetics of rapid formation and breakage of selectin-ligand bonds during the process of rolling of leukocytes on the endothelial wall.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism in L-Selectin, E-Selectin and ICAM-1 Genes in Asian Indian Pediatric Patients With Celiac Disease

et al. 2006

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Role of tumor necrosis factor receptors in an animal model of acute colitis

Cited by 48 publications

References 48 publications

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

IFN-γ and TNF-α decrease serotonin transporter function and expression in Caco2 cells

Polymorphism in L-Selectin, E-Selectin and ICAM-1 Genes in Asian Indian Pediatric Patients With Celiac Disease

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