This study identifies a long noncoding RNA (lncRNA), lincRNA-Cox2, which plays a crucial role in the regulation of inflammatory gene expression. LincRNA-Cox2 is induced by Toll-like receptors (TLRs) and mediates both the activation and repression of distinct classes of immune genes. The repression of target genes by lincRNA-Cox2 depends on its interaction with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. The study reveals that lincRNA-Cox2 is a broad-acting regulatory component of the inflammatory response circuit, highlighting its importance in the innate immune system. The findings also suggest that lncRNAs, such as lincRNA-Cox2, can act as both activators and repressors of gene expression, contributing to the complex regulation of inflammatory responses.This study identifies a long noncoding RNA (lncRNA), lincRNA-Cox2, which plays a crucial role in the regulation of inflammatory gene expression. LincRNA-Cox2 is induced by Toll-like receptors (TLRs) and mediates both the activation and repression of distinct classes of immune genes. The repression of target genes by lincRNA-Cox2 depends on its interaction with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. The study reveals that lincRNA-Cox2 is a broad-acting regulatory component of the inflammatory response circuit, highlighting its importance in the innate immune system. The findings also suggest that lncRNAs, such as lincRNA-Cox2, can act as both activators and repressors of gene expression, contributing to the complex regulation of inflammatory responses.