Inflammation is a protective response of cells to pathogens, infection or tissue damage. It involves the coordinated communication of different immune cells and blood vessels through an intricate cascade of molecular signals. Inflammation can cause fever, cardiovascular pathology, allergy anaphylaxis, fibrosis, autoimmunity, etc.

The inflammatory response has four phases: inflammatory inducers (infection or tissue damage), inflammatory sensors (mast cells and macrophages), inflammatory mediators (cytokines, chemokines, etc.) and the tissues that are affected [3]. Each phase has many options that are triggered based on the type pathogen introduced [1]. For example bacterial pathogens trigger toll-like receptors (TLRs) and viral infections trigger type I interferons (IFN[3].

In addition, chronic inflammatory conditions, where an inducer is not well defined, are becoming more common. These conditions are of particular interest because they coincide with other diseases such as obesity, type 2 diabetes, atherosclerosis, neurodengenerative diseases and cancer [3,4,5].

Thermo Scientific™ has a wide range of products to help with inflammatory response research.


Key Inflammatory Response Pathway Targets

Common targets in the inflammatory response pathway:

Aggrecan IFN-γ LFA-1 Th1
Angiopoietin-2 Ig Mac-1 Th2
BDNF IgA MCP-1/CCL2 Th9
CD23 IgE MCP-2/CCL8 Th17
CD30 IgG MCP-3/CCL7 Th22
CD40L IgM MIG/CXCL9 TLR 1
C-Reactive Protein IKK MIP-1α/CCL3 TLR 2
CTL IL-1 MIP-1β/CCL4 TLR 3
E-cadherin IL-2 MIP-2 TLR 4
EGF IL-3 NF-κB TLR 5
ELAM-1 IL-4 PAI-1 TLR 6
Eotaxin/CCL11 IL-5 PDGF-BB TLR 7
FGF basic IL-6 PECAM-1g TLR 8
G-CSF IL-8 p-Selectin TLR 9
GDNF IL-10 RANTES/CCL5 TLR 10
GM-CSF IL-12 SAA TNF-α
GRO-α IL-13 STAT1 TNF-β
HGF IL-15 STAT2 TGF-β1
HIF-1α IL-16 STAT3 TNF-RI
ICAM-1 IL-17 STAT4 TNF-RII
IFN-α IL-18 STAT5 VCAM-1
IFN-β IL-23 STAT6 VEGF

Three common transcription factors serve as key modulators in the inflammatory response pathway – nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), hypoxia-inducible factors-1 alpha (HIF-1α) and signal transducer and activator of transcription (STAT) . When inflammation becomes chronic these factors can lead to cancer [5]

NF-κB functions as the regulator of the acute phase of inflammation. The acute phase is where homeostastis is re-established after inflammatory induction. NF-κB acts by up regulating the expression of the cytokines that are inflammatory mediators. These cytokines include IL-1, IL-6, TNF-α, lymphotoxin and IFN-γ. In addition, IL-1 and TNF-α work to activate NF-κB, therefore creating a feedback loop [2].

HIF-1α plays a role in the cellular response to hypoxia. When oxygen levels decrease, HIF-1α induces transcription of genes that control processes such as angiogenesis and erythropoiesis. During inflammation, immune cells in the surrounding area experience a decrease in oxygen.  This decrease activates HIF1-α to help them survive longer. A number of cytokines, for example IL-1β, help HIF-1α to increase transcription. The use of the cytokines is mediated through NF-κB, which is shown to bind to HIF-1α promoters [6].

The STAT family of proteins serves multiple functions during inflammation depending on the type of inflammatory inducer. The type of inducer determines which cytokines are triggered. Those cytokines activate a STAT protein, which either increases or decreases inflammation. For instance, when the body comes into contact with a viral infection various IFNs are triggered and activate STAT1 and STAT2 that act in an anti-viral capacity to decrease inflammation. In contrast, STAT6 helps with differentiation of T helper cells. Subject to the type of differentiation, the T helper cells can positively influence allergic inflammation and negatively affect autoimmunity [7].

Data

Thermo Scientific™ offers antibodies, ELISAs, Luminex® multiplex assays and growth factors for key targets in the inflammatory response pathway. For more information please visit our Life Sciences Home Page.

Featured below are immunohistochemistry and immunofluorescence data using Thermo Scientific™ products.

human HeLa cells

Immunohistochemical analysis of formalin-fixed, paraffin-embedded human HeLa cells (top left) and LPS-stimulated HeLa cells (bottom left, right) using NF-κB p65-NLS rabbit polyclonal antibody (Product # PA5-23170).

Immunofluorescent analysis of STAT1 in MCF-7 Cells. Cells were grown on chamber slides and fixed with formaldehyde prior to staining. Cells were probed without (control) or with a STAT1 monoclonal antibody (Product # MA1-037), washed with PBS and incubated with a DyLight-488 conjugated secondary antibody (Product # 35503). STAT1 staining (green), F-Actin staining with Phalloidin (red) and nuclei with DAPI (blue) is shown.

References

  1. Medzhitov R. (2008) Origin and physiological roles of inflammation. Nature 454: 428-435.
  2. Ghosh S. et al (1998) NF-κB and rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16: 225-260.
  3. Medzhitov R. (2010) Inflammation 2010: new adventures of an old flame. Cell 140: 771-776.
  4. Bharat B. et al (2009) Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res 15(2): 425-430.
  5. Chiara P. et al (2009) Cellular and molecular pathways linking inflammation and cancer. Immunobiology 214(2009): 761-777.
  6. Scholz C. et al (2013) Targeting the HIF pathway in inflammation and immunity. Current Opinion in Pharamacology 13: 646-653.
  7. Kaplan, M. (2013) STAT signaling in inflammation. JAK-STAT 2: 1.

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Product Name Catalog Number
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Angiopoietin 2 Antibody
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CD154/CD40LG Antibody
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MCP-1 Antibody
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Eotaxin Antibody
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GRO alpha Antibody
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