Cold-inducible RNA-binding protein induces inflammatory responses via NF-κB signaling pathway in normal human bronchial epithelial cells infected with streptococcus pneumoniae

Community-acquired pneumonia causes significant illness and death worldwide, requiring further investigation and intervention. The invasion of Streptococcus pneumoniae (S. pneumoniae, S.p) can lead to serious conditions like meningitis, sepsis, or pneumonia. Extracellular Cold-inducible RNA-binding protein (eCIRP) acts as a damage-associated molecular pattern that triggers inflammatory responses and plays an important role in both acute and chronic inflammatory diseases. It remains unclear whether CIRP is involved in the process of S. pneumoniae infection in normal human bronchial epithelial cells (BEAS-2B). Cell counting kit (CCK)-8 assay was used to detect the activity of BEAS-2B cells. The subcellular localization of CIRP was detected by immunofluorescence. The mRNA and protein levels of CIRP, nuclear factor kappa-B (NF-κB) p65, toll like receptor-4 (TLR4), interleukin-6 (IL-6) were detected using quantitative real-time PCR (PCR) and Western Blot (WB). The protein expressions of CIRP, IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were assessed by enzyme-linked immunosorbent assay (ELISA). CIRP affects the activity of BEAS-2B cells induced by S. pneumoniae infection. After infection, CIRP translocates from the nucleus to the cytoplasm, thereby inducing the production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1). Additionally, the NF-κB p65 protein increases in infected cells but decreases with si-CIRP interference. Treatment with TLR4 neutralizing antibodies or NF-κB inhibitor effectively reduces the expressions of IL-1β, IL-6, TNF-α, and MCP-1. The infection with S. pneumoniae upregulates CIRP expression and translocates it from the nucleus to the cytoplasm in BEAS-2B cells, leading to the release of proinflammatory factors via activation of NF-κB signaling pathway. CIRP as a key mediator in S. pneumoniae-induced inflammation offers potential targets for therapeutic intervention against community-acquired pneumonia.