The main risk factor for
chronic obstructive pulmonary disease (
COPD) is cigarette
smoke (CS). It can alter many immune cells functions such as phagocytosis, efferocytosis and
cytokine production.
Cytokines play a role in the orchestration of
inflammation in
COPD. The JAK/STAT pathways are among the most important signalling components of
cytokines. The objective of this work was to investigate the role of the JAK/STAT pathway with regard to
cytokine release and
microsphere uptake capacity (to minimize the non-specific scavenging) in human monocyte-derived-macrophages (MDMs). The MDMs were stimulated by cigarette
smoke extract (CSE) alone or in combination with
lipopolysaccharide (LPS). CSE alone was not associated with significant changes in the
cytokine, with the exception of IL-8/CXCL8 production. However, CSE disturbed
cytokine production in LPS-stimulated MDMs. CSE increase CXCL-8 and CCL2 release in LPS-stimulated monocyte-derived macrophages and suppressed the production of
IL-6 and CXCL1 in these cells. CSE also decreased
microsphere uptake capacity by MDMs. Then, CSE + LPS-stimulated MDMs were treated with two different
JAK inhibitors.
AG490 (specific inhibitor of JAK2) and
ruxolitinib (inhibitor of JAK1 and JAK2). JAK/STAT inhibitors, particularly
ruxolitinib, attenuated in
cytokine production without completely inhibiting when compared with
dexamethasone. On the other hand, the cells exposed to
dexamethasone are nearly unable to capture the
microspheres, while both
JAK inhibitors do not affect the uptake capacity. In summary, our results showed the versatility of
ruxolitinib which might bring a better balance disturbance of
cytokine release and uptake capacity. The information regarding the distinctive effect of JAK/STAT inhibitors may be useful in the development of novel treatments for
COPD.