title: Calcitonin Peptide Family Members Are Differentially Regulated by LPS and Inhibit Functions of Rat Alveolar NR8383 Macrophages.
abstract: Members of the calcitonin peptide family-calcitonin gene-related peptide (CGRP), adrenomedullin (AM), and adrenomedullin2/intermedin (IMD)-exert modulatory effects upon monocytes and macrophages of various extrapulmonary origins. Utilizing the rat alveolar macrophage (AMφ) cell line NR8383, we here set out to determine to which extent these three peptides and their receptors are differentially regulated in AMφ and what specific effects they have on AMφ key functions. LPS treatment differentially up-regulated expression of the peptides and receptors. Among the three peptides, IMD mRNA content was lowest both in primary rat AMφ and NR8383 cells, whereas IMD peptide dominated in basal and LPS-stimulated secretion from NR8383 cells. Fcγ receptor-mediated phagocytosis and TNF-α production were inhibited by AM, IMD, and CGRP, whereas pro-IL-1β mRNA was slightly down-regulated exclusively by CGRP. Neither of these peptides affected IL-6 or IL-10 production. None increased intracellular calcium concentration, but AM significantly inhibited store-operated calcium entry. In conclusion, the rat AMφ cell line NR8383 is both a source and a target of the calcitonin peptide family members AM, IMD, and CGRP. Despite sharing proteins of the receptor complexes, AM, IMD, and CGRP each showed a characteristic pattern of effects and regulation, suggesting that these closely related peptides are not just redundant members of one common signaling pathway but act in concert by addressing parallel signaling cascades. Since peptide and receptor expression are up-regulated by LPS, these signaling pathways might act as inhibitory feedback mechanisms in pulmonary bacterial infection.
authors.affiliation: Institute for Anatomy and Cell Biology, Justus Liebig University, Giessen, Germany.
authors.forename: Aichurek
authors.initials: A
authors.lastname: Soultanova
authors.affiliation: Institute for Anatomy and Cell Biology, Justus Liebig University, Giessen, Germany.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Mikulski
authors.affiliation: Institute for Anatomy and Cell Biology, Justus Liebig University, Giessen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfeil
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus Liebig University, Giessen, Germany.|Excellence Cluster Cardiopulmonary System (ECCPS), German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
authors.affiliation: Institute for Anatomy and Cell Biology, Justus Liebig University, Giessen, Germany.|Excellence Cluster Cardiopulmonary System (ECCPS), German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D053607:Adrenomedullin / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation
chemical_list: C499411:Adm2 protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009479:Neuropeptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide