Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma

Tessier, Laurence; Côté, Olivier; Clark, Mary Ellen; Viel, Laurent; Diaz-Méndez, Andrés; Anders, Simon; Bienzle, Dorothee

doi:10.1186/s12864-017-4107-6

BMC Genomics

Table 3 The function of genes with overrepresented GO terms

From: Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma

Gene symbol	Positive regulation of immune system process	Immune response	Inflammatory response	Positive regulation of response to external stimulus	Secretion	Positive regulation of apoptotic signalling pathway	Neutrophil chemotaxis	Positive regulation of blood coagulation	Association with asthma	Protein function (NCBI or Uniprot; Homo sapiens)
S100A9	✓	✓	✓	✓	✓	✓	✓	✓	Promotes inflammation with and without TLR4 interactions in a mouse model [38]	Regulation of cellular processes such as cell cycle and differentiation. Antifungal and antibacterial activity
THBS1	✓	✓	✓	✓	✓	✓	×	✓	Central in a network linked to pulmonary response to oxidative stress in asthma [39]	Cell-to-cell and cell-to-matrix interactions
TLR4	✓	✓	✓	✓	✓	×	×	✓	Linked to allergic asthma in a mouse model [41]	Pathogen recognition and innate immunity
CXCL8	✓	✓	✓	✓	×	×	✓	×	Biomarker of neutrophilic asthma in adult [20]	Chemoattractant and angiogenic factor
C5AR1	✓	✓	✓	✓	×	×	✓	×	Linked to regulation of airway remodelling [42]	Receptor for C5a, ligand with chemotactic and inflammatory activity
MMP9	✓	✓	✓	×	✓	✓	×	×	Increased in severe asthma, involved in Th2 response and EMT in human bronchial epithelial cells [43, 44]	Matrix metalloproteinase, breakdown of extracellular matrix
NLRP12	✓	✓	✓	✓	✓	×	×	×	Increased expression in asthmatics on high-fat diet. No observed effect in allergic airway disease models [45,46,47]	Anti-inflammatory molecule
TREM1	✓	✓	×	×	✓	×	✓	×	Correlates with clinical stage and neutrophils in human asthmatics [48]	Amplifies neutrophil and monocyte inflammatory response
PLEK	✓	×	×	×	✓	×	×	✓	NA^a	EMT in bronchial epithelial cells [47]
LGALS3	✓	✓	×	×	×	×	✓	×	Key role in inflammation and airway remodelling in murine models of allergic asthma [95,96,97]. Decreased in sputum of neutrophilic asthmatics compared to mixed neutrophilic and eosinophilic asthmatics [98]	Involved in apoptosis, innate immunity, cell adhesion and T-cell regulation Antimicrobial activity
OSM	×	✓	×	✓	×	✓	×	×	Part of IL6 family of cytokines, OSM specifically is increased in asthmatics and correlates with irreversible airway obstruction [99]. OSM was associated with asthma but not atopy in children [100]	Inhibition of proliferation, regulation of production of other cytokines
PTGS2	×	×	✓	✓	✓	×	×	×	Polymorphism in the gene associated with asthma and atopy in children [101]	Prostaglandin biosynthesis
ORM1	✓	×	✓	×	✓	×	×	×	NA	Acute-phase protein, potential immunosuppressive activity
IL1RN	×	✓	✓	×	✓	×	×	×	Sputum IL1RN to IL-1β ratio decreased in neutrophilic asthmatics compared to mixed neutrophilic and eosinophilic asthmatics [98]	EMT in bronchial epithelial cells [47] Modulates IL1-mediated inflammation and inhibits activity of IL1A & B
CSF3R	✓	×	×	×	×	×	✓	×	NA	Controls granulocyte production and activity.
CXCR2	×	×	✓	×	×	×	✓	×	Expression increased in sputum of patient with non-eosinophilic asthma [21]. Controversial role in asthma. CXCR2 antagonists alone do not improve clinical signs of asthma but reduce neutrophil number [21]. Combination of CXCR1 and CXCR2 antagonists promising for therapy [102]	IL8 receptor, neutrophil migration
CAMP	×	✓	✓	×	×	×	×	×	NA	Response to pathogens, Antibacterial, regulation of cell chemotaxis and inflammation.
PTX3	×	✓	✓	×	×	×	×	×	Expression increased in bronchial tissues of asthmatics and highly expressed in smooth muscle cells [103]	Up-regulated in response to inflammation in epithelial cells. Role in angiogenesis and tissue remodelling.
MRGPRX2	×	✓	×	×	✓	×	×	×	NA	IgE independent activation of mast-cells, leading to inflammation and smooth muscle cell contraction [104]. Mast cell-specific receptor, mediates allergic reactions.
AQP9	×	✓	×	×	✓	×	×	×	NA	Neutrophil regulation [105]; membrane channel
CLEC4E	✓	✓	×	×	×	×	×	×	NA	Inflammation
LILRB3	✓	✓	×	×	×	×	×	×	NA	Inhibits immune response
CD300LB	✓	✓	×	×	×	×	×	×	NA	Expressed by granulocytes [106]. Activates immune receptor
Specific to one gene set
TNFRSF12A	×	×	×	×	×	✓	×	×	NA	May be involved in angiogenesis, proliferation and cellular adhesion
SFN	×	×	×	×	×	✓	×	×	NA	Regulation of protein kinase C [107] and epithelial cell growth through Akt/mTOR pathway when bound to KRT17 [108]
PLAUR	×	×	×	×	×	✓	×	×	Increased expression in vitro in bronchial epithelium from asthmatics [109]	Impaired wound repair process [109]. May be involved in plasminogen activation and ECM degradation
OLR1	×	×	✓	×	×	×	×	×	NA	Degradation of oxidized low-density lipoprotein
CCRL2	×	×	✓	×	×	×	×	×	Expressed in lung epithelial cells and up-regulated following LPS exposure. Potential role in initiation of allergic inflammation [110]	Unknown function, up-regulated in activated neutrophils
SERPINE2	×	×	×	×	✓	×	×	×	Urokinase inhibitor [111], overexpression in asthma and down-regulation correlated with improved FEV1 [112]	Serine protease inhibition
SRGN	×	×	×	×	✓	×	×	×	NA	Hematopoietic cell granule proteoglycan
TUBA4A	×	×	×	×	✓	×	×	×	NA	Component of microtubules
FCAR	×	✓	×	×	×	×	×	×	NA	Surface receptor of myeloid cells, regulation of immune defense processes
PADI4	×	✓	×	×	×	×	×	×	NA	Required for NET formation [79] in equine asthma [78], conversion of arginine to citrulline
APOBEC3B	×	✓	×	×	×	×	×	×	NA	Up-regulated by PKC and increased likelihood of mutations [113], RNA editing
TREML4	✓	×	×	×	×	×	×	×	NA	Immune response
CD300LD	✓	×	×	×	×	×	×	×	NA	Immune response
CD300A	✓	×	×	×	×	×	×	×	Co-aggregation of CD300A with CCR3 decreased clinical signs of asthma in a mouse model [114]	Regulation of mast cell response [115]. Surface protein on leukocytes involved in immune response
SLC46A2	✓	×	×	×	×	×	×	×	NA	Potential transporter function
SAMSN1	✓	×	×	×	×	×	×	×	NA	Cell proliferation, spreading and regulation of polarization
TREML2	✓	×	×	×	×	×	×	×	Associated with asthma but not atopy in children [100]	Surface receptor, role in innate and adaptive immune response

^a Not available

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ISSN: 1471-2164

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