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Effect of Linomide on adhesion molecules, TNF-alpha, nitrogen oxide, and cell adhesion.
Int Immunopharmacol. 2005 Feb; 5(2):231-9.II

Abstract

Linomide (quinoline-3-carboxamide) is an immunomodulator with anti-inflammatory effects in rodents with autoimmune diseases. Its mode of action still remains to be elucidated. We hypothesized that an investigation of T cell interactions with the extracellular matrix (ECM), composed of glycoproteins such as fibronectin (FN) and laminin (LN), might provide better understanding of their in vivo mode of action in extravascular inflammatory sites. We examined the effect of Linomide on T cell adhesion to intact ECM, and separately to LN, and FN, and on the release and production of tumor necrosis factor (TNFalpha) and nitrogen oxide (NO) in relation to adhesive molecules in non-obese diabetic (NOD) female spleen cells, focusing on intracellular adhesion molecule-1 (ICAM-1) and CD44. NOD female mice that developed spontaneous autoimmune insulitis, which destroys pancreatic islets and subsequently leads to insulin-deficient diabetes mellitus, were studied. Linomide, given in the drinking water or added to tissue cultures in vitro, inhibited the beta1 integrin-mediated adhesion of T cells to ECM, FN and LN, as well as the production and release of TNFalpha and NO, which play a major role in the induction and propagation of T cell-mediated insulitis. In addition, exposure of T cells to Linomide resulted in increased expression of CD44 and ICAM-1 molecules on spleen cells of Linomide-treated mice; such an increase in adhesion molecule expression may lead to more effective arrest of T cell migration in vivo. The regulation of T-cell adhesion, adhesion receptor expression, and inhibition of TNFalpha and NO secretion by Linomide may explain its beneficial role and provide a new tool for suppressing self-reactive T cell-dependent autoimmune diseases.

Authors+Show Affiliations

Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15652754

Citation

Abdul-Hai, A, et al. "Effect of Linomide On Adhesion Molecules, TNF-alpha, Nitrogen Oxide, and Cell Adhesion." International Immunopharmacology, vol. 5, no. 2, 2005, pp. 231-9.
Abdul-Hai A, Hershkoviz R, Weiss L, et al. Effect of Linomide on adhesion molecules, TNF-alpha, nitrogen oxide, and cell adhesion. Int Immunopharmacol. 2005;5(2):231-9.
Abdul-Hai, A., Hershkoviz, R., Weiss, L., Lider, O., & Slavin, S. (2005). Effect of Linomide on adhesion molecules, TNF-alpha, nitrogen oxide, and cell adhesion. International Immunopharmacology, 5(2), 231-9.
Abdul-Hai A, et al. Effect of Linomide On Adhesion Molecules, TNF-alpha, Nitrogen Oxide, and Cell Adhesion. Int Immunopharmacol. 2005;5(2):231-9. PubMed PMID: 15652754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Linomide on adhesion molecules, TNF-alpha, nitrogen oxide, and cell adhesion. AU - Abdul-Hai,A, AU - Hershkoviz,R, AU - Weiss,L, AU - Lider,O, AU - Slavin,S, PY - 2004/08/30/received PY - 2004/08/30/accepted PY - 2005/1/18/pubmed PY - 2005/6/29/medline PY - 2005/1/18/entrez SP - 231 EP - 9 JF - International immunopharmacology JO - Int Immunopharmacol VL - 5 IS - 2 N2 - Linomide (quinoline-3-carboxamide) is an immunomodulator with anti-inflammatory effects in rodents with autoimmune diseases. Its mode of action still remains to be elucidated. We hypothesized that an investigation of T cell interactions with the extracellular matrix (ECM), composed of glycoproteins such as fibronectin (FN) and laminin (LN), might provide better understanding of their in vivo mode of action in extravascular inflammatory sites. We examined the effect of Linomide on T cell adhesion to intact ECM, and separately to LN, and FN, and on the release and production of tumor necrosis factor (TNFalpha) and nitrogen oxide (NO) in relation to adhesive molecules in non-obese diabetic (NOD) female spleen cells, focusing on intracellular adhesion molecule-1 (ICAM-1) and CD44. NOD female mice that developed spontaneous autoimmune insulitis, which destroys pancreatic islets and subsequently leads to insulin-deficient diabetes mellitus, were studied. Linomide, given in the drinking water or added to tissue cultures in vitro, inhibited the beta1 integrin-mediated adhesion of T cells to ECM, FN and LN, as well as the production and release of TNFalpha and NO, which play a major role in the induction and propagation of T cell-mediated insulitis. In addition, exposure of T cells to Linomide resulted in increased expression of CD44 and ICAM-1 molecules on spleen cells of Linomide-treated mice; such an increase in adhesion molecule expression may lead to more effective arrest of T cell migration in vivo. The regulation of T-cell adhesion, adhesion receptor expression, and inhibition of TNFalpha and NO secretion by Linomide may explain its beneficial role and provide a new tool for suppressing self-reactive T cell-dependent autoimmune diseases. SN - 1567-5769 UR - https://www.unboundmedicine.com/medline/citation/15652754/Effect_of_Linomide_on_adhesion_molecules_TNF_alpha_nitrogen_oxide_and_cell_adhesion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(04)00275-9 DB - PRIME DP - Unbound Medicine ER -