You are hereNews

News


Anti-TNFα Therapy in Inflammatory Lung Diseases bn.

Jeffrey D. Laskin, Ph.D. - Thu, 07/20/2017 - 02:00

Related Articles

Anti-TNFα Therapy in Inflammatory Lung Diseases bn.

Pharmacol Ther. 2017 Jun 19;:

Authors: Malaviya R, Laskin JD, Laskin DL

Abstract
Increased levels of tumor necrosis factor (TNF) α have been linked to a number of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sarcoidosis, and interstitial pulmonary fibrosis (IPF). TNFα plays multiple roles in disease pathology by inducing an accumulation of inflammatory cells, stimulating the generation of inflammatory mediators, and causing oxidative and nitrosative stress, airway hyperresponsiveness and tissue remodeling. TNF-targeting biologics, therefore, present a potentially highly efficacious treatment option. This review summarizes current knowledge on the role of TNFα in pulmonary disease pathologies, with a focus on the therapeutic potential of TNFα-targeting agents in treating inflammatory lung diseases.

PMID: 28642115 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung.

Paul J. Lioy, Ph.D. - Thu, 07/20/2017 - 02:00

Related Articles

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung.

Exp Mol Pathol. 2017 Feb;102(1):50-58

Authors: Sunil VR, Vayas KN, Fang M, Zarbl H, Massa C, Gow AJ, Cervelli JA, Kipen H, Laumbach RJ, Lioy PJ, Laskin JD, Laskin DL

Abstract
Exposure to World Trade Center (WTC) dust has been linked to respiratory disease in humans. In the present studies we developed a rodent model of WTC dust exposure to analyze lung oxidative stress and inflammation, with the goal of elucidating potential epigenetic mechanisms underlying these responses. Exposure of mice to WTC dust (20μg, i.t.) was associated with upregulation of heme oxygenase-1 and cyclooxygenase-2 within 3days, a response which persisted for at least 21days. Whereas matrix metalloproteinase was upregulated 7days post-WTC dust exposure, IL-6RA1 was increased at 21days; conversely, expression of mannose receptor, a scavenger receptor important in particle clearance, decreased. After WTC dust exposure, increases in methylation of histone H3 lysine K4 at 3days, lysine K27 at 7days and lysine K36, were observed in the lung, along with hypermethylation of Line-1 element at 21days. Alterations in pulmonary mechanics were also observed following WTC dust exposure. Thus, 3days post-exposure, lung resistance and tissue damping were decreased. In contrast at 21days, lung resistance, central airway resistance, tissue damping and tissue elastance were increased. These data demonstrate that WTC dust-induced inflammation and oxidative stress are associated with epigenetic modifications in the lung and altered pulmonary mechanics. These changes may contribute to the development of WTC dust pathologies.

PMID: 27986442 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members