title: MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection.
abstract: BACKGROUND
  Caseous lymphadenitis (CL) is a contagious infectious disease of small ruminants caused by Corynebacterium pseudotuberculosis. Is characterized by the formation of abscesses in the lymph nodes and intestines of infected animals, induced by inflammatory cytokines. The production of cytokines, such as IL-10, TNF-α, IL-4 and IFN-γ, is regulated by mitogen-activated protein kinase (MAPK) pathway activation. The present study investigated the involvement of MAPK pathways (MAPK p38, ERK 1 and ERK 2) with respect to the production of cytokines induced by antigens secreted by C. pseudotuberculosis over a 60-day course of infection. CBA mice (n = 25) were divided into three groups and infected with 102 colony forming units (CFU) of attenuated strain T1, 102 CFU of virulent strain VD57 or sterile saline solution and euthanized after 30 or 60 days. Murine splenocytes were treated with specific inhibitors (MAPK p38 inhibitor, ERK 1/2 inhibitor or ERK 2 inhibitor) and cultured with secreted antigens obtained from pathogenic bacteria (SeT1 or SeVD57).
  
  
  RESULTS
  The MAPK pathways evaluated were observed to be involved in the production of IL-10, under stimulation by secreted antigens, while the MAPK p38 and ERK 1 pathways were shown to be primarily involved in TNF-α production. By contrast, no involvement of the MAPK p38 and ERK 1 and 2 pathways was observed in IFN-γ production, while the ERK 2 pathway demonstrated involvement in IL-4 production only in the mouse splenocytes infected with VD57 under stimulation by SeT1.
  
  
  CONCLUSIONS
  The authors hypothesize that MAPK p38 and ERK 1 pathways with respect to TNF-α production, as well as the MAPK p38 and ERK 1 and 2 pathways in relation to IL-10 production under infection by C. pseudotuberculosis are important regulators of cellular response. Additionally, the lack of the MAPK p38 and ERK 1/2 pathways in IFN-γ production in infected CBA murine cells stimulated with the two secreted/excreted antigens, in IL-4 production showing involvement only via the ERK 2 pathway under stimulation by SeT1 antigen during 60-day infection period with the virulent strain, suggests that these pathways regulated the production of pro-inflammatory and regulatory cytokines in the splenic cells of CBA mice.
authors.affiliation: Biointeraction Department - Immunology and Molecular Biology Laboratory - Health Sciences Institute (ICS), Federal University of Bahia (UFBA), Av, Reitor Miguel Calmon, s/n; Vale do Canela, Salvador CEP 40040-040, Bahia, Brazil. andreia.pachecosouza@yahoo.com.br.
authors.forename: Andréia Pacheco
authors.initials: AP
authors.lastname: de Souza
authors.forename: Vera Lúcia Costa
authors.initials: VL
authors.lastname: Vale
authors.forename: Marcos da Costa
authors.initials: Mda C
authors.lastname: Silva
authors.forename: Inara Barbosa de Oliveira
authors.initials: IB
authors.lastname: Araújo
authors.forename: Soraya Castro
authors.initials: SC
authors.lastname: Trindade
authors.forename: Lília Ferreira
authors.initials: LF
authors.lastname: de Moura-Costa
authors.forename: Gabriele Costa
authors.initials: GC
authors.lastname: Rodrigues
authors.forename: Tatiane Santana
authors.initials: TS
authors.lastname: Sales
authors.forename: Heidiane Alves
authors.initials: HA
authors.lastname: dos Santos
authors.forename: Paulo Cirino
authors.initials: PC
authors.lastname: de Carvalho-Filho
authors.forename: Milton Galdino
authors.initials: MG
authors.lastname: de Oliveira-Neto
authors.forename: Robert Eduard
authors.initials: RE
authors.lastname: Schaer
authors.forename: Roberto
authors.initials: R
authors.lastname: Meyer
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D003354:Corynebacterium Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D016925:Corynebacterium pseudotuberculosis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008808:Mice, Inbred CBA; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D020928:Mitogen-Activated Protein Kinases