Protein-protein interaction studies revealed a close interaction among CCL27 and CXCL13 but not CCL15. A summary of serum concentrations is provided in Table 2.
In silico analysis did not exhibit any interaction of CCL15 within this cascade and therefore is not included in the protein-protein network.
Analysis of the serum cytokine and chemokine panel in the biomass-exposed group revealed higher levels of CCL15 (inflammatory), CCL27 (homeostatic), and CXCL13 (homeostatic) in BMS-CONTROL subjects compared to BMS-COPD.
Wellemans et al., "Expression and regulation of CCL15 by human airway smooth muscle cells," Clinical & Experimental Allergy, vol.
IGFBP-1: Insulin-like growth factor-binding protein 1 IGFBP-2: Insulin-like growth factor-binding protein 2 BDNF: Brain-derived neurotrophic factor L-Selectin: CD62L E-Selectin: CD62E ICAM-1: Intercellular adhesion molecule 1 PECAM: Platelet endothelial cell adhesion molecule VCAM-1: Vascular cell adhesion protein 1 MIP-1d: Chemokine (C-C motif) ligand 15 (CCL15
) MIP-3b: Macrophage inflammatory protein-3 (CCL19) Eotaxin-1: C-C motif chemokine 11 (CCL11) Eotaxin-2: Chemokine (C-C motif) ligand 24 (CCL24) BLC: B lymphocyte chemoattractant.
In a similar manner, SF-derived exosomes induced the release of several chemokines (CCL8, CCL15, CCL20, and CXCL1), while downregulating the production of others (CCL7 in particular; Figures 4(a) and 4(c)).
In our study, we also observed that SF-derived exosomes are able to stimulate the production of CCL20, CCL15, and CXCL1 chemokines by M1 macrophages.
Some of these were present in more than 3 samples: growth factors (fibroblast growth factor 4, placental growth factor), chemotactic factors [B lymphocyte chemoattractant/CXCL13, macrophage inflammatory protein (MIP)-1[beta]/CCL4, MIP-1[delta]/ CCL15
, MIP-3[alpha]/CCL20, pulmonary and activation-related chemokine (PARC)/CCL18, leukemia inhibitory factor, oncostatin M], and antiinflammatory factors [tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, macrophage-derived chemokine (MDC)/CCL22].
The recruitment of MDSCs into tumor sites is primarily mediated by various cancer cells that produce chemokines, including CCL2, CCL15
, CXCL5, and CXCL12 [61-64].
Multiple chemokines have been reported to be upregulated in the CSF of patients with pneumococcal meningitis including CCL15
, CXCL7, MIF, CCL8, CCL18, CCL20, CXCL5, CXCL-1, CXCL-8, CCL2, CCL3, and CCL4 [78-81].
Genes expressed more highly in OECs were Jagged 1 (JAG1), JAG2, placental growth factor (PGF), endothelial cell-specific molecule 1 (ESM1), neurite growth-promoting factor 2 (MDK), inhibin beta A (INHBA), growth differentiation factor-3 (GDF3), pre-B-cell colony-enhancing factor 1 (PBEF1), endothelin 1 (EDN1), interleukin 32 (IL32), heparin-binding EGF-like growth factor (HBEGF), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 2 (CCL2), CCL14, CCL15, bone morphogenetic protein 2 (BMP2), BMP4, and BMP6, whereas genes expressed more highly in MSCs were wingless-type MMTV integration site family, member 5A (WNT5A), CXCL5, vascular endothelial growth factor (VEGF), CCL20, angiopoietin 1 (ANGPT1), growth differentiation factor 5 (GDF5), and WNT5B (Figure 7).
Based on gene expression profiling, we found that MSCs showed high gene expression of WNT5A, CXCL5, VEGF, CCL20, ANGPT1, GDF5, and WNT5B, whereas OECs showed high gene expression of JAG1, JAG2, PGF, ESM1, MDK, INHBA, GDF3, PBEF1, EDN1, IL32, HBEGF, CXCL1, CCL2, CCL14, CCL15, BMP2, BMP4, and BMP6.