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Inhibition of NF-kappaB by IkappaB prevents cytokine-induced NO production and promotes enterocyte apoptosis in vitro.
Shock 2000; 14(3):366-73S

Abstract

Nuclear factor-kappaB (N-kappaB) plays a key role in gut inflammation. NF-kappaB up-regulates proinflammatory genes encoding cytokines, adhesion molecules, and inducible nitric oxide synthase (iNOS). However, NF-kappaB has also been shown to up-regulate protective or anti-apoptotic factors. We utilized an adenoviral vector carrying a super-repressor form of the inhibitor of NF-kappaB, IkappaB, to examine the effects of NF-kappaB inhibition on cytokine-induced nitric oxide production and apoptosis in rat small intestinal epithelial cells (IEC-6). Chemical inhibitors of NF-kappaB, including pyrrolidine dithiocarbamate (PDTC), tosyl-lysine-chloromethylketone (TLCK), genistein, and N-acetyl-leu-leu-norleucinal (n-LLnL) were also utilized. Treatment of AdIkappaB-transfected cells with cytomix [1000 U/mL IFN-gamma, 1 nM IL-1beta, and 10 ng/mL tumor necrosis factor alpha (TNFalpha)] or TNFalpha-containing cytokine combinations resulted in inhibition of cytokine-induced nitrite production and a marked increase in apoptosis compared to control cells. Apoptosis occurred independently of nitric oxide (NO) production since exogenous sources of NO did not inhibit apoptosis. Inducible NOS and clAP were down-regulated in AdIkappaB-transfected cells treated with cytomix. TLCK and LLnL treatment also induced apoptosis in cytomix-treated cells, while PDTC and genistein did not. Thus, although NF-kappaB up-regulates various pro-inflammatory genes, it may also have protective or anti-apoptotic effects in enterocytes. NF-kappaB appears necessary for upregulating cIAP in IEC-6 cells upon cytokine exposure.

Authors+Show Affiliations

Department of Surgery, Children's Hospital of Pittsburgh and the University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11028558

Citation

Potoka, D A., et al. "Inhibition of NF-kappaB By IkappaB Prevents Cytokine-induced NO Production and Promotes Enterocyte Apoptosis in Vitro." Shock (Augusta, Ga.), vol. 14, no. 3, 2000, pp. 366-73.
Potoka DA, Nadler EP, Zhou X, et al. Inhibition of NF-kappaB by IkappaB prevents cytokine-induced NO production and promotes enterocyte apoptosis in vitro. Shock. 2000;14(3):366-73.
Potoka, D. A., Nadler, E. P., Zhou, X., Zhang, X. R., Upperman, J. S., & Ford, H. R. (2000). Inhibition of NF-kappaB by IkappaB prevents cytokine-induced NO production and promotes enterocyte apoptosis in vitro. Shock (Augusta, Ga.), 14(3), pp. 366-73.
Potoka DA, et al. Inhibition of NF-kappaB By IkappaB Prevents Cytokine-induced NO Production and Promotes Enterocyte Apoptosis in Vitro. Shock. 2000;14(3):366-73. PubMed PMID: 11028558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of NF-kappaB by IkappaB prevents cytokine-induced NO production and promotes enterocyte apoptosis in vitro. AU - Potoka,D A, AU - Nadler,E P, AU - Zhou,X, AU - Zhang,X R, AU - Upperman,J S, AU - Ford,H R, PY - 2000/10/12/pubmed PY - 2001/6/8/medline PY - 2000/10/12/entrez SP - 366 EP - 73 JF - Shock (Augusta, Ga.) JO - Shock VL - 14 IS - 3 N2 - Nuclear factor-kappaB (N-kappaB) plays a key role in gut inflammation. NF-kappaB up-regulates proinflammatory genes encoding cytokines, adhesion molecules, and inducible nitric oxide synthase (iNOS). However, NF-kappaB has also been shown to up-regulate protective or anti-apoptotic factors. We utilized an adenoviral vector carrying a super-repressor form of the inhibitor of NF-kappaB, IkappaB, to examine the effects of NF-kappaB inhibition on cytokine-induced nitric oxide production and apoptosis in rat small intestinal epithelial cells (IEC-6). Chemical inhibitors of NF-kappaB, including pyrrolidine dithiocarbamate (PDTC), tosyl-lysine-chloromethylketone (TLCK), genistein, and N-acetyl-leu-leu-norleucinal (n-LLnL) were also utilized. Treatment of AdIkappaB-transfected cells with cytomix [1000 U/mL IFN-gamma, 1 nM IL-1beta, and 10 ng/mL tumor necrosis factor alpha (TNFalpha)] or TNFalpha-containing cytokine combinations resulted in inhibition of cytokine-induced nitrite production and a marked increase in apoptosis compared to control cells. Apoptosis occurred independently of nitric oxide (NO) production since exogenous sources of NO did not inhibit apoptosis. Inducible NOS and clAP were down-regulated in AdIkappaB-transfected cells treated with cytomix. TLCK and LLnL treatment also induced apoptosis in cytomix-treated cells, while PDTC and genistein did not. Thus, although NF-kappaB up-regulates various pro-inflammatory genes, it may also have protective or anti-apoptotic effects in enterocytes. NF-kappaB appears necessary for upregulating cIAP in IEC-6 cells upon cytokine exposure. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/11028558/Inhibition_of_NF_kappaB_by_IkappaB_prevents_cytokine_induced_NO_production_and_promotes_enterocyte_apoptosis_in_vitro_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11028558.ui DB - PRIME DP - Unbound Medicine ER -