TNFα-induced macrophage chemokine secretion is more dependent on NF-κB expression than lipopolysaccharides-induced macrophage chemokine secretion

Abstract

The transcription factor NF‐κB is a pivotal intracellular regulator of many inflammatory responses and it has been proposed that it represents a potential therapeutic target. As chemokines are important for the progress of an inflammatory response by the recruitment of immuno‐competent cells, the role NF‐κB plays in TNFα‐ or lipopolysaccharides (LPS)‐induced chemokine secretion by human monocyte‐derived macrophages was examined. Secretion of the CXC chemokines IL‐8, GROα and ENA‐78, induced by TNFα, was significantly suppressed by inhibiting NF‐κB, using overexpression of IκBα. However, when induced by LPS the expression of these chemokines was unaffected. In contrast, expression of the CC chemokines MIP‐1α, MCP‐1 and RANTES inducedby TNFα or LPS was significantly inhibited by the overexpression of IκBα. Therefore, there appear to be different mechanisms regulating CC and CXC chemokine secretion by macrophages, depending on the stimulus and that TNFα and LPS can use different signaling mechanisms in macrophages to regulate chemokine synthesis.

Heterogeneous requirement of IκB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: Implications for therapy

“…For passaged synovial fibroblasts, an MOI of 500 was used because these cells are more resistant to adenovirus infection. These MOIs have been previously shown by us and others to result in Ͼ90% of these cells expressing the transgene of interest (17,35,41,42,45).…”

Activation of NF-κB by the intracellular expression of NF-κB-inducing kinase acts as a powerful vaccine adjuvant

“…Interestingly, IL-1␤ and IP-10 that also contain NF-B sites in their promoters were not induced by NIK. As IL-1␤ is NF-B-dependent and IP-10 is IRF3-dependent but NF-Bindependent in many but not all systems (38,39), our data suggest that all of the signals required for the expression of these genes cannot be compensated by NIK alone.…”

“…Adenoviruses encoding GFP, ␤-gal, NIK, MyD88, IKK2, MEKK-1, and I B␣ are E1͞E3-deleted, belong to the Ad5 serotype, and have been described (13,14,39). The adenoviruses for IKK2dn and I B␣ were kind gifts of R. De Martin (University of Vienna, Vienna, Austria), and the adenovirus for ␤-gal was from M. Wood (University of Oxford, Oxford, U.K.).…”

Toll-Like Receptor (TLR)2 and TLR4 Agonists Regulate CCR Expression in Human Monocytic Cells

“…These processes are heavily dependent upon chemokines and their receptors. Monocytes and cells derived from them, such as macrophages and dendritic cells (DCs), 3 are critical to the innate immune system and provide important bridges into adaptive immunity through both the regulated generation of proinflammatory cytokines and their ability to present Ag. Disease-specific variations in inflammatory infiltrates have been reported.…”

“…For example in arthritides, infiltrates contain mainly cells of the monocyte lineage (1) that produce members of the CC chemokine family, and the recruitment of these cells is in turn controlled by CC chemokines (2). Multiple agonists can influence the expression of chemokines, including bacterial products and proinflammatory cytokines (3). In contrast to the wide belief that cytokines such as IL-1 and TNF-␣ are the main proinflammatory mediators induced by bacterial stimulants, chemokine genes show the highest induction in human monocytes in response to both Gram-positive and Gram-negative bacteria and their components (4,5).…”