J Occup Med Toxicol. 2016 Sep 21;11:46. doi: 10.1186/s12995-016-0135-4. eCollection 2016.
Fungal cell wall agents and bacterial lipopolysaccharide in organic dust as possible risk factors for pulmonary sarcoidosis.
Journal of occupational medicine and toxicology (London, England)
Sanja Stopinšek, Alojz Ihan, Barbara Salobir, Marjeta Terčelj, Saša Simčič
Affiliations
Affiliations
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia.
- Department for Respiratory and Allergic Diseases, University Medical Centre, Zaloška 2, SI-1000 Ljubljana, Slovenia.
PMID: 27688795
PMCID: PMC5031305 DOI: 10.1186/s12995-016-0135-4
Abstract
BACKGROUND: Composition of organic dust is very complex, involving particles of microbial, animal and plant origin. Several environmental exposure studies associate microbial cell wall agents in organic dust with various respiratory symptoms and diseases. The aim of the present study was to investigate the in vitro effects of the co-exposure of fungal cell wall agents (FCWAs) and bacterial lipopolysaccharide (LPS) on inflammatory immune responses of peripheral blood mononuclear cells (PBMCs) from patients with pulmonary sarcoidosis.
METHODS: PBMCs from 22 patients with pulmonary sarcoidosis and 20 healthy subjects were isolated and stimulated in vitro with FCWAs (soluble and particulate (1 → 3)-β-D-glucan, zymosan and chitosan) and/or LPS. Subsequently, cytokines were measured by ELISA and the mRNA expression of dectin-1, toll-like receptor 2 (TLR2), TLR4 and mannose receptor (MR) was analysed by real-time RT-PCR.
RESULTS: Patients with sarcoidosis had a significantly higher secretion of inflammatory cytokines tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-10 and IL-12 (1.7-fold, 2.0-fold, 2.2-fold, and 2.8-fold, respectively; all p < 0.05) after in vitro co-stimulation of PBMCs with FCWAs and LPS. We showed that PBMCs from patients with sarcoidosis had a higher baseline mRNA expression of dectin-1, TLR2, TLR4 and MR (6-fold, 11-fold, 18-fold, and 4-fold, respectively). Furthermore, we found a reduced expression of dectin-1, TLR2 and TLR4 after stimulation with FCWAs and/or LPS, although the reduction was significantly weaker in patients than in healthy subjects.
CONCLUSIONS: In conclusion, co-stimulation with FCWAs and LPS of PBMC from patients with sarcoidosis caused a weaker reduction of dectin-1, TLR2, TLR4 receptors expression, which could increase the sensitivity of PBMCs, leading to excessive inflammatory cytokine responses and result in the development or progression of pulmonary sarcoidosis.
Keywords: (1 → 3)-β-D-glucan; Cytokines; Fungi; LPS; PBMC; Pattern-recognition receptors; Sarcoidosis
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