title: Corticotropin-releasing hormone receptor-1 and 2 activity produces divergent resistance against stress-induced pulmonary Streptococcus pneumoniae infection.
abstract: Utilizing a murine model of S. pneumoniae infection and restraint stress, we determined how corticotropin releasing hormone (CRH-R) receptors impacts disease. CRH-R1 (antalarmin) and CRH-R2 (astressin2B) antagonists were administered intraperitoneally prior to restraint stress followed by pulmonary S. pneumoniae infection. CRH-R1 inhibition is not protective against pneumococcal disease induced by stress. Conversely, CRH-R2 inhibition attenuates stress-induced bacterial growth and significantly prevented severe sepsis. Neutrophillic responses were associated with CRH receptor-specific disease outcome providing a potential cellular target for stress-induced susceptibility to the development of severe pneumococcal disease. CRH receptor-mediated effects on immune responses could prove valuable for novel therapeutics.
authors.affiliation: Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
authors.forename: Byung-Jin
authors.initials: BJ
authors.lastname: Kim
authors.forename: Kay
authors.initials: K
authors.lastname: Kayembe
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Simecka
authors.forename: Mark
authors.initials: M
authors.lastname: Pulse
authors.forename: Harlan P
authors.initials: HP
authors.lastname: Jones
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011008:Pneumococcal Infections / Q000276:immunology* / Q000523:psychology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology*; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control / Q000523:psychology; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013315:Stress, Psychological / Q000276:immunology; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1