title: Altered expression of the CCN genes in the lungs of mice in response to cigarette smoke exposure and viral and bacterial infections.
abstract: The CCN proteins are key signaling and regulatory molecules involved in many biological functions and contribute to malignant and non-malignant lung diseases. Despite the high morbidity and mortality of the lung respiratory infectious diseases, there is very little data related to the expression of the CCNs during infection. We investigated in mice the pulmonary mRNA expression levels of five CCNs (1 to 5) in response to influenza A virus (IAV) and bacterial agents (Nontypeable Haemophilus influenzae (NTHi), lipopolysaccharide (LPS) and lipoteichoic acid (LTA)). IAV, NTHi, LPS or LTA were instilled intranasally into mice. Mice were also exposed for 4days or 8weeks to cigarette smoke alone or prior infection to IAV in order to determine if CS modifies the CCN response to a viral infection. All challenges induced a robust inflammation. The mRNA expression of CCN1, CCN2 and CCN3 was decreased after short exposure to CS whereas prolonged exposure altered the expression of CCN1, CCN3 and CCN4. Influenza A virus infection increased CCN1, 2, 4 and 5 mRNA levels but expression of CCN3 was significantly decreased. Acute CS exposure prior infection had little effect on the expression of CCN genes but prolonged exposure abolished the IAV-dependent induction. Treatment with LPS or LTA and infection with NTHi revealed that both Gram-positive and Gram-negative bacteria rapidly modulate the expression of the CCN genes. Our findings reveal that several triggers of lung inflammation influence differently the CCN genes. CCN3 deserves special attention since its mRNA expression is decreased by all the triggers studied.
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gueugnon
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France.
authors.forename: Virginie C
authors.initials: VC
authors.lastname: Thibault
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kearley
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Petit-Courty
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Vallet
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Guillon
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.affiliation: INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, Tours, France; Université François Rabelais, Tours, France. Electronic address: courty@univ-tours.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Courty
mesh_terms: D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000276:immunology*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000502:physiology; D009980:Influenza A virus / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055514:Nephroblastoma Overexpressed Protein / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012907:Smoking
chemical_list: D055511:CCN Intercellular Signaling Proteins; C491850:CCN1 protein, mouse; C526318:CCN2 protein, mouse; C492067:CCN4 protein, mouse; C568642:CCN6 protein, mouse; C526320:Ccn3 protein, mouse; D055515:Cysteine-Rich Protein 61; D047908:Intracellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D011518:Proto-Oncogene Proteins; C539089:WISP-2 protein, mouse; D055513:Connective Tissue Growth Factor
keywords: Inflammation; Influenza virus; Matricellular proteins; Mice model; Nontypeable Haemophilus influenzae