Pulmonary neutrophilia caused by absence of the NF-κB member RelB is dampened by exposure to cigarette smoke. (October 2019)

• Record Type: Journal Article
• Authors: Pareek, Swati; Traboulsi, Hussein; Allard, Benoit; Rico de Souza, Angela; Eidelman, David H.; Baglole, Carolyn J.
• Is Part Of: Molecular immunology. Volume 114(2019:Oct.)
• Page Start: 395
• Page End: 409
• Publication Date: 2019-10
• Subjects: Lung -- Cigarette smoke -- Inflammation -- Neutrophil -- NF-kB; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.08.011
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Absence of the NF-κB family member RelB reduces pulmonary neutrophilia from acute cigarette smoke exposure. RelB does not regulate inflammation from other common inhalational toxicants. The way RelB controls pulmonary neutrophila from smoke may be via regulation of CX3CR1. RelB exerts immunoregulatory functions in the respiratory system to modulate the level of inflammation. Abstract: Inflammation is a response to injury and infection. Although protective under physiological conditions, excessive and persistent inflammation is linked to numerous diseases. As the lungs are continuously exposed to the external environment, the respiratory system is particularly liable to damage from inflammation. RelB is a member of the non-canonical NF-κB pathway that may control lung inflammation caused by cigarette smoke (CS), a leading cause of morbidity and mortality worldwide. Our lab has previously shown that RelB protects against CS-induced inflammation in vitro, leading us to hypothesize that RelB would protect against acute CS-induced pulmonary inflammation in vivo . We exposed wild-type ( Relb +/+ ) and RelB-deficient mice (Relb −/− ) mice to room air or to CS and found that CS exposure caused a sustained decrease in pulmonary granulocytes in Relb −/− mice that was predominated by a decrease in neutrophils. Pulmonary inflammation caused by other irritants, including chlorine, ovalbumin (OVA; to mimic features of asthma) and lipopolysaccharide (LPS) was not controlled by RelB. Differential cytokine analysis suggests that alterations in chemotactic cytokines do not fully account for the CS-specific decrease in neutrophils in Relb −/− mice. Flow cytometric analysis of the bronchoalveolar lavage and bone marrow cells also reveal that it is unlikely that the sustained decrease is caused by excessive cell death or decreased hematopoiesis from the bone marrow. Overall, our results indicate that RelB regulates acute CS-induced pulmonary inflammation. Understanding how RelB regulates CS-induced inflammation may potentiate the discovery of new therapeutic strategies for many of the inflammatory diseases caused by CS.