550:
IL-34 induces lung fibrosis via M2 macrophages differentiation in mouse lung injured model
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Munehiro Yamaguchi, MD PhD
RATIONALE:

IL-34 was recent discovered cytokine and is known ligand that binds to CSF-1 receptor, thereby enhancing tissue macrophage maturation and differentiation. Expression of IL-34 with in the lung was evident, but the localization and the expressing cells were not so far unclear. Also, M2 macrophages are known to play critical role in fibrotic disorders such as NAFLD (Non-alcoholic fatty liver disease). Therefore, we hypothesized that lung epithelial cells derived IL-34 was released and may influence lung fibrosis via M2 macrophage induction.

METHODS:

C57/BL6 Wt mice were exposed LPS or LPS + recombinant (r-) IL-34 intratracheally on day 0 and mice were sacrificed on day 1, 3, 5, 7. Bronchoalveolar lavage (BAL) fluid were collected . BAL was analyzed for total and differential cell counts. Protein levels of cytokines within BAL and lung tissue were measured by ELISA. Expression and localization of IL-34 in lung tissues were deteced with immunohistochemistry (IHC). Furthermore, M2 macrophages were analyzed by qPCR. THP-1 cells and Beas-2b cells were co-cultured with medium in vitro and Supernatant and cells were collected for expression of cytokines using ELISA and qPCR.

RESULTS:

IL-34 expression of lung tissue and BAL was increased on day 1 and was detected in lung epithelium in the LPS treated mice. LPS stimulated THP-1 cells released TNF-alpha and furthermore TNF-alpha stimulated Beas-2b cells inducing IL-34. Also, IL-34 altered M0 macrophages to M2 macrophages using in vitro model.

CONCLUSIONS:

Induction of epithelial derived IL-34 may enhance lung fibrosis via M2 macrophages alteration in lung injury mouse model