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Transgenic Up‐Regulation Of Claudin‐6 Decreases Diesel Particulate Matter (DPM)‐Induced Pulmonary Inflammation
Author(s) -
Bodine Jared,
Gassman Jason,
Milner Dallin C.,
Lewis Adam,
Dunaway Todd,
Egbert Kaleb,
Christiansen Connor,
Christiansen Andrew,
Monson Troy,
Broberg Dallin,
Arroyo Juan,
Reynolds Paul R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.305.11
Subject(s) - inflammation , claudin , bronchoalveolar lavage , genetically modified mouse , lung , inhalation exposure , microbiology and biotechnology , immunology , transgene , chemistry , tight junction , inhalation , medicine , biology , gene , biochemistry , anatomy
Cldn6 is a tetraspanin transmembrane protein found in tight junctional complexes and is implicated in maintaining lung epithelial barriers. In the present study, we tested the hypothesis that abundant Cldn‐6 influences inflammation in mice exposed to acute environmental diesel particulate matter (DPM). Mice were subjected to ten exposures of nebulized DPM over a period of 20 days via a nose only inhalation system (Sireq industries). Using real time RT‐PCR, we discovered that the Cldn6 gene was up‐regulated in control mice exposed to DPM but DPM significantly decreased Cldn‐6 expression in lung‐specific transgenic mice that up‐regulate Cldn‐6 (Cldn‐6 TG). DPM caused increased cell diapedesis into bronchoalveolar lavage fluid (BALF) obtained from control mice, however, Cldn‐6 TG mice had less total cells in BALF following DPM exposure. Because Cldn‐6 TG mice diminished cell diapedesis, other inflammatory intermediates were screened in order to characterize the impact of increased Cldn‐6 on inflammation. In summary, MAPKs, NF‐kB and cytokines including TNF‐alpha and IL‐1beta were all differentially regulated in Cldn6 TG mice and controls following DPM exposure. These results demonstrate that epithelial barriers organized by Cldn‐6 mediate, at least in part, diesel‐induced inflammation. Further work may show that Cldn‐6 is a key target in understanding pulmonary epithelial gateways exacerbated by environmental pollution. Support or Funding Information This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).