Aug 2026· Developmental and Comparative Immunology· pp.
105720
· 0 citations· 66 references
Medicine
TL;DR
It is indicated that CRP and SAP have evolved distinct subcellular localization and regulatory functions, with CRP fine-tuning the NF-κB/TNFα axis and SAP promoting an IL-4-associated response.
Abstract
C-reactive protein (CRP) and serum amyloid P component (SAP) are evolutionarily conserved soluble pattern-recognition molecules that play critical roles in innate immunity, but their functional divergence in teleosts remains poorly understood. Here we characterized the CRP and SAP homologs in spotted sea bass (Lateolabrax maculatus) and investigated their distinct immunomodulatory functions. The full-length cDNAs of CRP and SAP encode proteins of 230 and 224 amino acids, respectively, both containing typical pentraxin domains with conserved motifs. Both genes were constitutively expressed, with CRP predominant in the brain and SAP in the spleen. Following challenge with lipopolysaccharide (LPS), Poly (I:C), or Edwardsiella tarda, both genes were significantly upregulated in vivo and in vitro, confirming their identity as acute-phase proteins. Subcellular localization in spotted sea bass brain (LMB) cells and HEK-293T cells revealed distinct patterns: CRP was predominantly perinuclear, whereas SAP was enriched in the nucleus, suggesting non-canonical intracellular functions. Functional overexpression in LMB cells further demonstrated divergent roles: CRP suppressed TNFα while upregulating NF-κB1 and NF-κB2, whereas SAP specifically induced IL-4 and NF-κB1. These findings indicate that CRP and SAP have evolved distinct subcellular localization and regulatory functions, with CRP fine-tuning the NF-κB/TNFα axis and SAP promoting an IL-4-associated response. This study provides new insights into the functional diversification of pentraxins in teleost immunity.
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