Impact of fatty acid binding protein 5‐deficiency on COPD exacerbations and cigarette smoke‐induced inflammatory response to bacterial infection

Abstract

BackgroundAlthough cigarette smoking (CS) is by far the most important risk factor of chronic obstructive pulmonary disease (COPD), repeated and sustained infections are clearly linked to disease pathogenesis and are responsible for acute inflammatory flares (i.e. COPD exacerbations). We have previously identified Fatty Acid Binding Protein 5 (FABP5) as an important anti‐inflammatory protein in primary airway epithelial cells. ResultsIn this study we found decreased FABP5 mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) of COPD patients, especially among those who reported episodes of COPD exacerbations. Using wildtype (WT) and FABP5−/− mice, we examined the effects of FABP5 on CS and infection‐induced inflammatory responses. Similarly to what we saw in airway epithelial cells, infection increased FABP5 expression while CS decreased FABP5 expression in mouse lung tissues. CS‐exposed and P. aeruginosa‐infected FABP5−/− mice had significantly increased inflammation as shown by increased lung histopathological score, cell infiltration and inflammatory cytokine levels. Restoration of FABP5 in alveolar macrophages using a lentiviral approach attenuated the CS‐ and bacteria‐induced pulmonary inflammation. And finally, while P. aeruginosa infection increased PPARγ activity, CS or FABP5 knockdown greatly reduced PPARγ activity. ConclusionsThese findings support a model in which CS‐induced FABP5 inhibition contributes to increased inflammation in COPD exacerbations. It is interesting to speculate that the increased inflammation is a result of decreased PPARγ activity.

Fatty acid-binding protein 5 limits ILC2-mediated allergic lung inflammation in a murine asthma model

“…FABP5 is involved in the pathogenesis of viral/bacterial lung infection and the airway inflammation in allergic asthmatics 15 , 16 , 22 . To evaluate the precise role of FABP5 in allergic lung inflammation, we intranasally administrated recombinant IL-33, one of the cytokines known to cause lung inflammation through ILC2 activation, into mice and examined lung inflammation in wild-type and Fabp5 −/− mice.…”

“…FABP5 in alveolar epithelial cells is responsible for RA synthesis during allergic lung inflammation. As mentioned above, FABP5 is expressed on a variety of lung cells [15][16][17] . Immunostaining with EpCAM or CD11c and FABP5 showed that the FABP5 + cells overlapped with the EpCAM + or CD11c + cells in lung tissue (Fig.…”

MicroRNA-30d-5p ameliorates lipopolysaccharide-induced acute lung injury via activating AMPKα

“…Fresh lung tissues were homogenized and mixed with 1 ml Trizol reagent for total RNA extraction, which was then reversely transcribed to cDNA using the first-strand cDNA synthesis kit as previously described [24][25][26][27]. The qRT-PCR was performed using SYBR Green Mix and the melting curve analysis was performed to examine the specificity of the primer sequence and amplification.…”

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