The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases

Table 1

S100 proteins involved in pulmonary diseases.

Protein	Receptor and interacting proteins	Major cells expressing	Pulmonary disease	Study
S100A1	RAGE	Macrophages, dendritic, epithelial, and endothelial cells	Reduced in pulmonary hypertension	[61]
S100A2	RAGE	Cancer cells, basal, club and ciliated cells	Reported both induced and reduced in non-small-cell lung carcinoma	[71]
S100A3	RAGE, retinoid receptor, RARα, and PML-RARα	Endothelial, epithelial, and lymphatic cells	Reduced in both pulmonary fibrosis and lung cancer models	[72]; [74]
S100A4	TLR4, IL-10R, EGFR, ErbB4, HSPG, GPCR, and RAGE	Tumor cells, T cells, neutrophils, and macrophages	Increased in both lung NSCLC and pulmonary fibrosis	[77]; [79]
S100A5	RAGE	Macrophages and cancer cells	Increased in nonsmoking NSCLC	[84]
S100A6	RAGE	Most lung cells but predominantly neutrophils, macrophages, and NK cells	Increased in lung cancer cells, idiopathic pulmonary fibrosis, sarcoidosis, and COPD; Reduced in CF	[90]; [95]; [95]; [95]; [94]
S100A7	RAGE	Epithelial cells and neutrophils	Reduced in rhinosinusitis; Increased in lung NSCLC, squamous cell cancer, asthma, bacterial-associated exacerbations, and pulmonary involvement in systemic sclerosis	[100]; [98, 105, 219, 220]; [99]; [102]; [101]
S100A8	TLR4, heparan sulfate and N-glycans, S100A9, and RAGE	Many tissues but predominantly monocytes, granulocytes, and epithelial cells	Increased in cystic fibrosis, extracellular levels in COPD, chronic tuberculosis, asthma, acute lung injury, restrictive allograft syndrome, and COVID-19; Reduced intracellular levels in COPD	[93]; [107, 109]; [116]; [118]; [112]; [121]; [136, 137]
S100A9	TLR4, heparan sulfate and N-glycans, RAGE, S100A8, and EMMPRIN	Many cell types but predominantly macrophages, granulocytes, and epithelial cells	Increased in COPD with and without AE, cystic fibrosis, lung cancer, chronic tuberculosis, IPF, acute, exacerbations, asthma, acute lung injury, restrictive allograft syndrome, rhinosinusitis, and COVID-19	[39, 108–110]; [93]; [122, 221]; [116]; [123, 124]; [118–120]; [112, 125]; [121]; [125]; [136, 137]
S100A10	GPCRs, serotonin receptors, CCR10, and AnxA2	Many cell types but predominantly macrophages, granulocytes, and epithelial cells	Increased in lung adenocarcinoma, hypertension, and acute lung injury	[129, 130]; [126]; [127]
S100A11	RAGE	Ubiquitous expression in various tissues and cell types	Increased in lung adenocarcinoma, hypertension, idiopathic pulmonary fibrosis, sarcoidosis, and COPD	[131, 222]; [223]; [95]; [95]; [95]
S100A12	TLR4, RAGE, N-glycans, scavenger receptors, and GPCR	Granulocytes and monocytes	Increased in asthma, COPD, ARDS, restrictive allograft syndrome, and COVID-19	[134, 135]; [109]; [224]; [121]; [136, 137]
S100A13	RAGE	Ubiquitous expression in various tissues and cell types	Increased in pulmonary fibrosis and lung cancer cells	[72]; [75, 225]
S100A14/S100A11P	RAGE	Epithelial cells and cancer cells	Increased in lung adenocarcinoma and NSCLC	[139, 226, 227]
S100A15	GPCR	Cancer cells and neutrophils	Increased in lung adenocarcinoma	[140]
S100A16	Unknown receptor interaction but binds to S100A14	Cancer, epithelial, endothelial cells, and fibroblasts	Increased in lung adenocarcinoma and NSCLC	[141, 142]
S100B	RAGE and FGFR1	Cancer cells, dendritic cells, and lymphocytes	Increased in lung SCL but reduced in NSCLC	[145]; [84]
S100G	Annexin A10	Epithelial and cancer cells	Increased in lung NSCLC	[84]
S100P	RAGE and p53	Epithelial and cancer cells	Increased in restrictive allograft syndrome, lung NSCLS, adenocarcinoma, and pulmonary arterial hypertension	[121]; [146, 148, 149]; [150]
S100Z	S100A1, S100A3, and S100B	Monocytes and dendritic cells	No known pulmonary link