Support
icon_0328_cc_gen_hmr_bacteria-s

IL-12 Signaling and Production in Macrophages

Interleukin 12 (IL-12p70 or IL-12) is a heterodimeric pro-inflammatory cytokine produced by macrophages that are activated by pathogens or T lymphocytes. IL-12p70 is comprised of the monomeric subunits p40 and p35. The IL-12p40 monomer can homodimerize, or, heterodimerize with another monomer p19 giving rise to the IL-12 related cytokines: IL-12p80 and IL-23. In addition to producing IL-12, macrophages also respond to it; thus IL-12 demonstrates an autocrine effect in macrophages and other cell types like dendritic cells. The signaling by IL-12 is effected through heterodimeric IL-12 receptors (IL-12R)...

IL-12 Signaling and Production in Macrophages

Pathway Summary

Interleukin 12 (IL-12p70 or IL-12) is a heterodimeric pro-inflammatory cytokine produced by macrophages that are activated by pathogens or T lymphocytes. IL-12p70 is comprised of the monomeric subunits p40 and p35. The IL-12p40 monomer can homodimerize, or, heterodimerize with another monomer p19 giving rise to the IL-12 related cytokines: IL-12p80 and IL-23. In addition to producing IL-12, macrophages also respond to it; thus IL-12 demonstrates an autocrine effect in macrophages and other cell types like dendritic cells. The signaling by IL-12 is effected through heterodimeric IL-12 receptors (IL-12R). The IL-12R protein composed of β1 and β2 chains is found on resting macrophages; however expression of these chains is upregulated during cell activation.One of the major effects of IL-12 signaling on macrophages is the induction of interferon gamma (IFN γ) which in turn favors the differentiation of T helper 1 cells (TH1) cells, affecting the development of adaptive immunity. IL-12-induced production of interferon gamma (IFN γ) by macrophages is dependent on signal transducers and activators of transcription 4 (STAT4). The cytokine IL-18 secreted by several cell types including macrophages, synergizes with IL-12 in the production of IFN γ by activating nuclear translocation of STAT4. In addition, this synergy also increases the production of nitric oxide, which in turn promotes intracellular bacterial death. Complex reciprocal influences take place between IL-12 and IFN γ , both of which are involved in the initiation of cell-mediated immunity. IFN γ can enhance the expression of IL-12Rβ1 thereby increasing the number of IL-12 binding sites expressed on macrophages. Autocrine production of IL-12 seems to be another major effect of IL-12 on macrophages, which is reinforced in the presence of IFN γ. In addition to IFN γ, IL-12p40 monomer or IL-12p80 induce the tumor necrosis factor (TNF). This induction is triggered by the mitogen activated protein kinase (MAPK) pathway leading to the activation of factors like CCAAT/enhancer binding protein (C/EBP) and NF kappa B (NF-κB), which increase the gene expression of TNF. Thus IL-12 serves as a bridge between innate and adaptive immunity: Macrophages produce IL-12 when they encounter a pathogen. The signaling by IL-12 in macrophages, in turn, produces cytokines like IFN γ and TNF, which develop the TH1 response, thereby enhancing adaptive immunity.The subunits of IL-12, IL-12p40 and IL-12p35 are expressed from separate genes on different chromosomes. Both genes need to be expressed coordinately for the production of IL-12. The expression of IL-12p35 is constitutive and ubiquitous. On the other hand, IL-12p40 is expressed in cells like macrophages only upon activation. The transcription of IL-12p40 gene is thus regulated by a number of factors. Signaling via the toll like receptor (TLR) that is activated by several bacterial structural components, is one major mechanism that upregulates the transcription of the IL-12p40 gene. Stimulation of TLRs triggers the MAPK pathway in several ways. This stimulation could activate transcription factors like C/EBP, activator protein 1 (AP-1) and NF-κB, which in turn enhance transcription. The NF-κB mediated upregulation of IL-12p40 gene expression is enhanced by nuclear factors like steroid receptor coactivator-1 (SRC-1), p300 and PU.1 and inhibited by nuclear receptors like retinoid X receptor (RXR) and peroxisome proliferator activated receptor gamma (PPARγ). Signaling by IFN γ also enhances the transcription of the IL-12p40 gene via a STAT1/ interferon stimulated factor (IRF8) mechanism in conjunction with IRF-1.This pathway highlights the important components of IL-12 signaling and production in macrophages.

IL-12 Signaling and Production in Macrophages Genes list

Explore Genes related to IL-12 Signaling and Production in Macrophages

Products related to IL-12 Signaling and Production in Macrophages

Explore products related to IL-12 Signaling and Production in Macrophages
GeneGlobe ID: PAHS-150Z | Cat. No.: 330231 | RT2 Profiler PCR Arrays
RT² Profiler™ PCR Array Human Cytokines & Chemokines
RT2 Profiler PCR Array
Product Specification
GeneGlobe ID: PAHS-021Z | Cat. No.: 330231 | RT2 Profiler PCR Arrays
RT² Profiler™ PCR Array Human Common Cytokines
RT2 Profiler PCR Array
Product Specification
GeneGlobe ID: SBHS-150Z | Cat. No.: 249950 | QuantiNova LNA PCR Focus Panels
QuantiNova LNA PCR Focus Panel Human Cytokines & Chemokines
QuantiNova LNA PCR Focus Panel
Product Specification
GeneGlobe ID: SBHS-021Z | Cat. No.: 249950 | QuantiNova LNA PCR Focus Panels
QuantiNova LNA PCR Focus Panel Human Common Cytokines
QuantiNova LNA PCR Focus Panel
Product Specification
GeneGlobe ID: UPHS-150Z | Cat. No.: 249955 | QuantiNova LNA Probe PCR Focus Panels
QuantiNova LNA Probe PCR Focus Panel Human Cytokines & Chemokines
QuantiNova LNA Probe PCR Focus Panel
Product Specification
GeneGlobe ID: UPHS-021Z | Cat. No.: 249955 | QuantiNova LNA Probe PCR Focus Panels
QuantiNova LNA Probe PCR Focus Panel Human Common Cytokines
QuantiNova LNA Probe PCR Focus Panel
Product Specification

Didn't find what you're looking for?

Discover other products relevant to this gene list with our Panel Finder. Check it out.