Silica‐carrying particulate matter enhances Bjerkandera adusta‐induced murine lung eosinophilia

Abstract

Bjerkandera adusta (B. adusta) causes fungus-associated chronic cough. However, the inflammatory response is not yet fully understood. Recently, B. adusta was identified in Asian sand dust (ASD) aerosol. This study investigated the enhancing effects of ASD on B. adusta-induced lung inflammation. B. adusta was inactivated by formalin. ASD was heated to remove toxic organic substances. ICR mice were intratracheally instilled with saline, B. adusta 0.2 µg, or B. adusta 0.8 µg with or without heated ASD 0.1 mg (H-ASD), four times at 2-week intervals. Two in vitro experiments were conducted to investigate any enhancing effects using bone marrow-derived macrophages (BMDM) from Toll-like receptor (TLR) knockout mice and ICR mice. Co-exposure to H-ASD and B. adusta, especially at high doses, caused eosinophil infiltration, proliferation of goblet cells in the airway, and fibrous thickening of the subepithelial layer, and remarkable increases in expression of Th2 cytokines and eosinophil-related cytokine and chemokine expression in bronchoalveolar lavage fluid. In the in vitro study using BMDM from wild-type, TLR2-/-, and TLR4-/- mice, the TLR-signaling pathway for cytokine production caused by B. adusta was predominantly TLR2 rather than TLR4. H-ASD increased the expression of NF-κB and cytokine production by B. adusta in BMDM from ICR mice. The results suggest that co-exposure to H-ASD and B. adusta caused aggravated lung eosinophilia via remarkable increases of pro-inflammatory mediators. The aggravation of inflammation may be related, at least in part, to the activation of the TLR2-NF-κB signaling pathway in antigen presenting cells by H-ASD.

Occupational and Environmental Contributions to Chronic Cough in Adults

“…Mechanisms There are many examples and potential mechanisms by which occupational and environmental factors may cause or exacerbate an acute or chronic cough, as summarized in Table 1. Direct effects of particulates or gas may be to stimulate cough receptors or directly induce asthma, [4][5][6] and it is possible that direct effects of noxious chemicals such as ammonia, through trigeminal nerve stimulation, may increase awareness of the sensation (although this relation specifically to cough has not been substantiated). 7 Indirect effects of occupational dust and allergens are strongly associated with secondary infectious or noninfectious sinusitis, bronchitis, and cough-variant asthma, with stimulation of the cough triggered by inflammatory mediators or by direct neurogenic stimulation.…”

The Role of Toll-Like Receptors and Myeloid Differentiation Factor 88 in <b><i>Bjerkandera adusta-</i></b>Induced Lung Inflammation

“…In accordance with these clinical studies, our recent experimental research showed that B. adusta alone caused an eosinophil-rich pulmonary inflammatory response and Th2 cytokine [such as interleukin (IL)-5] production in mice, as well as increased inflammatory molecule secretion from bone marrow-derived macrophages (BMDM) in vitro [12]. We also found that B. adusta caused eosinophilic airway inflammation and aggravated ovalbumin-induced murine lung eosinophilia along with fibrous thickening of the subepithelial layer [13].…”

“…WT, TLR2 -/- , TLR4 -/- , TLR2/4 -/- , TLR7/9 -/- , and MyD88 -/- mice (on a C57BL/6J background, n = 4/genotype) were purchased from Oriental Bioservice [12]. Femurs were removed at 8 weeks of age, and soft tissue was removed and flushed with Hanks' solution to recover the bone marrow.…”

“…The degree of thickening of the subepithelial layer in the main bronchus was graded on the following scale: 0, not present; 1, slight; 2, mild; 3, moderate; 4, moderate to marked, and 5, marked. ‘Slight' was defined as 5-12 μm of the main bronchus with fibroblasts stained with PAS; ‘mild' as 13-20 μm; ‘moderate' as 21-28 μm; ‘moderate to marked' as 29-36 μm, and ‘marked' as more than 37 μm [12,13]. …”

Co-exposure to zymosan A and heat-inactivated Asian sand dust exacerbates ovalbumin-induced murine lung eosinophilia

“…The TLR4 ligand lipopolysaccharide (LPS) and TLR2 ligands such as β-glucan are strong candidates for causing the exacerbation of lung eosinophilia by ASD [ 21 ]. An in vitro study showed that TLR2 rather than TLR4 contributes to the production of pro-inflammatory cytokines from bone marrow-derived macrophages [ 23 ]. On the basis of these results, we speculated that ASD-adherent β-glucan is one of the exacerbating factors of lung eosinophilia.…”