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Pasteurella haemolytica leukotoxin and endotoxin induced cytokine gene expression in bovine alveolar macrophages requires NF-kappaB activation and calcium elevation.
Microb Pathog. 1999 May; 26(5):263-73.MP

Abstract

In bovine alveolar macrophages (BAMs), exposure to leukotoxin (Lkt) and endotoxin (LPS) from Pasteurella haemolytica results in expression of inflammatory cytokine genes and intracellular calcium ([Ca2+]i) elevation. Leukotoxin from P. haemolytica interacts only with leukocytes and platelets from ruminant species. Upregulation of cytokine genes in different cells by LPS involves activation of the transcription factor NF-kappaB (NF-kappaB), resulting in its translocation from the cytoplasm to the nucleus. Using immunocytochemical staining and confocal imaging, we studied whether NF-kappaB activation represents a common mechanism for the expression of multiple cytokine genes in BAMs (Lkt-susceptible cells) stimulated with Lkt and LPS. Bovine pulmonary artery endothelial cells and porcine alveolar macrophages were used as nonsusceptible cells. The role of Ca2+ and tyrosine kinases in NF-kappaB activation and inflammatory cytokine gene expression was studied, since an inhibitor of tyrosine kinases attenuates LPS-induced [Ca2+]i elevation in BAMs. The results are summarized as follows: (a) Lkt induced NF-kappaB activation and [Ca2+]i elevation only in BAMs, while LPS effects were demonstrable in all cell types; (b) chelation of [Ca2+]i blocked NF-kappaB activation and IL-1beta, TNFalpha, and IL-8 mRNA expression; and (c) tyrosine kinase inhibitor herbimycin A blocked expression of all three cytokine genes in BAMs stimulated with Lkt, while only the expression of IL-1beta was blocked in BAMs stimulated with LPS. We conclude that cytokine gene expression in BAMs requires NF-kappaB activation and [Ca2+]i elevation, and Lkt effects exhibit cell type- and species specificity.

Authors+Show Affiliations

Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10222211

Citation

Hsuan, S L., et al. "Pasteurella Haemolytica Leukotoxin and Endotoxin Induced Cytokine Gene Expression in Bovine Alveolar Macrophages Requires NF-kappaB Activation and Calcium Elevation." Microbial Pathogenesis, vol. 26, no. 5, 1999, pp. 263-73.
Hsuan SL, Kannan MS, Jeyaseelan S, et al. Pasteurella haemolytica leukotoxin and endotoxin induced cytokine gene expression in bovine alveolar macrophages requires NF-kappaB activation and calcium elevation. Microb Pathog. 1999;26(5):263-73.
Hsuan, S. L., Kannan, M. S., Jeyaseelan, S., Prakash, Y. S., Malazdrewich, C., Abrahamsen, M. S., Sieck, G. C., & Maheswaran, S. K. (1999). Pasteurella haemolytica leukotoxin and endotoxin induced cytokine gene expression in bovine alveolar macrophages requires NF-kappaB activation and calcium elevation. Microbial Pathogenesis, 26(5), 263-73.
Hsuan SL, et al. Pasteurella Haemolytica Leukotoxin and Endotoxin Induced Cytokine Gene Expression in Bovine Alveolar Macrophages Requires NF-kappaB Activation and Calcium Elevation. Microb Pathog. 1999;26(5):263-73. PubMed PMID: 10222211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pasteurella haemolytica leukotoxin and endotoxin induced cytokine gene expression in bovine alveolar macrophages requires NF-kappaB activation and calcium elevation. AU - Hsuan,S L, AU - Kannan,M S, AU - Jeyaseelan,S, AU - Prakash,Y S, AU - Malazdrewich,C, AU - Abrahamsen,M S, AU - Sieck,G C, AU - Maheswaran,S K, PY - 1999/5/1/pubmed PY - 1999/5/1/medline PY - 1999/5/1/entrez SP - 263 EP - 73 JF - Microbial pathogenesis JO - Microb Pathog VL - 26 IS - 5 N2 - In bovine alveolar macrophages (BAMs), exposure to leukotoxin (Lkt) and endotoxin (LPS) from Pasteurella haemolytica results in expression of inflammatory cytokine genes and intracellular calcium ([Ca2+]i) elevation. Leukotoxin from P. haemolytica interacts only with leukocytes and platelets from ruminant species. Upregulation of cytokine genes in different cells by LPS involves activation of the transcription factor NF-kappaB (NF-kappaB), resulting in its translocation from the cytoplasm to the nucleus. Using immunocytochemical staining and confocal imaging, we studied whether NF-kappaB activation represents a common mechanism for the expression of multiple cytokine genes in BAMs (Lkt-susceptible cells) stimulated with Lkt and LPS. Bovine pulmonary artery endothelial cells and porcine alveolar macrophages were used as nonsusceptible cells. The role of Ca2+ and tyrosine kinases in NF-kappaB activation and inflammatory cytokine gene expression was studied, since an inhibitor of tyrosine kinases attenuates LPS-induced [Ca2+]i elevation in BAMs. The results are summarized as follows: (a) Lkt induced NF-kappaB activation and [Ca2+]i elevation only in BAMs, while LPS effects were demonstrable in all cell types; (b) chelation of [Ca2+]i blocked NF-kappaB activation and IL-1beta, TNFalpha, and IL-8 mRNA expression; and (c) tyrosine kinase inhibitor herbimycin A blocked expression of all three cytokine genes in BAMs stimulated with Lkt, while only the expression of IL-1beta was blocked in BAMs stimulated with LPS. We conclude that cytokine gene expression in BAMs requires NF-kappaB activation and [Ca2+]i elevation, and Lkt effects exhibit cell type- and species specificity. SN - 0882-4010 UR - https://www.unboundmedicine.com/medline/citation/10222211/Pasteurella_haemolytica_leukotoxin_and_endotoxin_induced_cytokine_gene_expression_in_bovine_alveolar_macrophages_requires_NF_kappaB_activation_and_calcium_elevation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0882-4010(98)90271-6 DB - PRIME DP - Unbound Medicine ER -