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Systemic IL-6 Effector Response in Mediating Systemic Bone Loss Following Inhalation of Organic Dust.


ABSTRACT: Airway and skeletal diseases are prominent among agriculture workers. Repetitive inhalant exposures to agriculture organic dust extract (ODE) induces bone deterioration in mice; yet the mechanisms responsible for connecting the lung-bone inflammatory axis remain unclear. We hypothesized that the interleukin (IL)-6 effector response regulates bone deterioration following inhalant ODE exposures. Using an established intranasal inhalation exposure model, wild-type (WT) and IL-6 knockout (KO) mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx, cytokine/chemokine release, and lung pathology were not reduced in IL-6 KO animals compared to WT mice. Utilizing micro-computed tomography, analysis of tibia showed that loss of bone mineral density, volume, and deterioration of bone micro-architecture, and mechanical strength induced by inhalant ODE exposures in WT mice were absent in IL-6 KO animals. Compared to saline treatments, bone-resorbing osteoclasts and bone marrow osteoclast precursor populations were also increased in ODE-treated WT but not IL-6 KO mice. These results show that the systemic IL-6 effector pathway mediates bone deterioration induced by repetitive inhalant ODE exposures through an effect on osteoclasts, but a positive role for IL-6 in the airway was not demonstrated. IL-6 might be an important link in explaining the lung-bone inflammatory axis.

SUBMITTER: Wells A 

PROVIDER: S-EPMC5240004 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Systemic IL-6 Effector Response in Mediating Systemic Bone Loss Following Inhalation of Organic Dust.

Wells Adam A   Romberger Debra J DJ   Thiele Geoffrey M GM   Wyatt Todd A TA   Staab Elizabeth E   Heires Art J AJ   Klassen Lynell W LW   Duryee Michael J MJ   Mikuls Ted R TR   Dusad Anand A   West William W WW   Wang Dong D   Poole Jill A JA  

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 20161122 1


Airway and skeletal diseases are prominent among agriculture workers. Repetitive inhalant exposures to agriculture organic dust extract (ODE) induces bone deterioration in mice; yet the mechanisms responsible for connecting the lung-bone inflammatory axis remain unclear. We hypothesized that the interleukin (IL)-6 effector response regulates bone deterioration following inhalant ODE exposures. Using an established intranasal inhalation exposure model, wild-type (WT) and IL-6 knockout (KO) mice w  ...[more]

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