PMID- 9862717 OWN - NLM STAT- MEDLINE DCOM- 19990122 LR - 20201219 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 161 IP - 12 DP - 1998 Dec 15 TI - Lymphotoxin alpha3 induces chemokines and adhesion molecules: insight into the role of LT alpha in inflammation and lymphoid organ development. PG - 6853-60 AB - Lymphotoxin (LT) plays an important role in inflammation and lymphoid organ development, though the mechanisms by which it promotes these processes are poorly understood. Toward this end, the biologic activities of a recently generated recombinant murine (m) LT alpha preparation were evaluated. This cytokine preparation was effective at inducing cytotoxicity of WEHI target cells with 50% maximal killing observed with 1.2 ng/ml. mLT alpha also induced the expression of inflammatory mediators in the murine endothelial cell line bEnd.3. rmLT alpha induced expression of the adhesion molecules VCAM, ICAM, E-selectin, and the mucosal addressin cellular adhesion molecule, MAdCAM-1. When mLT alpha, human (h) LT alpha, and mTNF-alpha were compared, mLT alpha was the most potent inducer of MAdCAM-1. None of these cytokines induced the peripheral node addressin, PNAd. mLT alpha also induced expression of the chemokines RANTES, IFN-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1). mRNA levels peaked 4 h following treatment with mLT alpha and declined through the 24-h treatment period. LT alpha also induced chemokine protein within 8 h of treatment, which increased through the 24-h treatment period. These data demonstrate that the proinflammatory effects of LT alpha3 may be mediated in part through the induction of adhesion molecule and chemokine expression. Further, LT alpha3 may promote development of lymphoid tissue through induction of chemokines and the mucosal addressin MAdCAM-1. These data confirm previous observations in transgenic and knockout mice that LT alpha3 in the absence of LT beta carries out unique biologic activities. FAU - Cuff, C A AU - Cuff CA AD - Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA. FAU - Schwartz, J AU - Schwartz J FAU - Bergman, C M AU - Bergman CM FAU - Russell, K S AU - Russell KS FAU - Bender, J R AU - Bender JR FAU - Ruddle, N H AU - Ruddle NH LA - eng GR - 5 T32 AI 07019-20/AI/NIAID NIH HHS/United States GR - AI 34404/AI/NIAID NIH HHS/United States GR - CA 16885/CA/NCI NIH HHS/United States GR - etc. PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL4) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL2) RN - 0 (Chemokines) RN - 0 (Chemokines, CXC) RN - 0 (E-Selectin) RN - 0 (Immunoglobulins) RN - 0 (Lymphotoxin-alpha) RN - 0 (MADCAM1 protein, human) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Madcam1 protein, mouse) RN - 0 (Monokines) RN - 0 (Mucoproteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Animals MH - Cell Adhesion Molecules/*biosynthesis/genetics MH - Chemokine CCL2/biosynthesis/genetics MH - Chemokine CCL4 MH - Chemokine CCL5/biosynthesis/genetics MH - Chemokine CXCL10 MH - Chemokine CXCL2 MH - Chemokines/*biosynthesis/genetics MH - Chemokines, CXC/biosynthesis/genetics MH - Cytotoxicity, Immunologic MH - E-Selectin/biosynthesis/genetics MH - Embryonic and Fetal Development MH - Gene Expression Regulation/*drug effects MH - Humans MH - Immunoglobulins/biosynthesis/genetics MH - Inflammation/*physiopathology MH - Intercellular Adhesion Molecule-1/biosynthesis/genetics MH - Lymphoid Tissue/*embryology MH - Lymphotoxin-alpha/chemistry/*pharmacology/physiology MH - Macrophage Inflammatory Proteins/biosynthesis/genetics MH - Mice MH - Monokines/biosynthesis/genetics MH - Mucoproteins/biosynthesis/genetics MH - Recombinant Fusion Proteins/pharmacology MH - Species Specificity MH - Stimulation, Chemical MH - Tumor Cells, Cultured MH - Vascular Cell Adhesion Molecule-1/biosynthesis/genetics EDAT- 1998/12/23 00:00 MHDA- 1998/12/23 00:01 CRDT- 1998/12/23 00:00 PHST- 1998/12/23 00:00 [pubmed] PHST- 1998/12/23 00:01 [medline] PHST- 1998/12/23 00:00 [entrez] PST - ppublish SO - J Immunol. 1998 Dec 15;161(12):6853-60.