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Signaling Pathways  Inflammation pathways, a biological response to harmful stimuli

Inflammation pathways constitute the adaptive response to various stimuli (toxins, viruses, bacteria, ischemia, or necrotic tissue, trauma ...) that surrounds us. It is part of the body's defense mechanism.
The immune system moderates this biological response via a series of signaling pathways. This includes the proteins such as pro- and anti-inflammatory factors. Failure of this process results in significant adverse effects and can become pathogenic (1,5).

There are two important types of inflammatory response: acute and chronic inflammation (2).

  • Acute or short-lived, promotes cell survival. During this phase, T cells produce cytokines such as IL-6 and tumor necrosis factor-α (TNF-α). These trigger the activation of numerous of inflammatory pathways. This includes, nuclear factor kappa-B (NF-κB) pathway, mitogen-activated protein kinase (MAPK) pathway, and Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway are activated.
  • Chronic or long-lasting activated when immune cells are unable to eliminate pathogens. This leads to a series of diseases, generally considered to be a fundamental disease state. During this phase, abnormal occurrences of cytokines increases the development of acute reactants and other media. Diseases linked to this phase include obesity, insulin resistance and type 2 diabetes (T2D).

Signaling Pathways title  Inflammation pathways and diseases

Chronic inflammatory response is the main cause of a wide range of diseases. Among them, neurodegenerative disorders like Alzheimer and aging. Besides psychiatric disorders including major depression, schizophrenia and bipolar disorder. In addition to malignant tumors, atherosclerosis, heart diseases, rheumatoid arthritis, pulmonary disease, asthma, periodontitis, inflammatory bowel disease, psoriasis...
Inflammatory response promotes disease through many mechanisms, including the inflammasome, senescent cells, the microbiota, the activation of microglia and localized infection (5-9).
Loss of immune regulation between protective and impaired responses can lead to coronavirus disease 2019 (COVID-19). This due to exacerbation of the inflammatory components.

Cytokine storm characterize SARS-CoV-2 infection. This includes high levels of IL-6, IL-12 and IL-1β, and tumor necrosis factor (TNF). In addition to defective type I interferon activity (3,9).

Inflammation_and_COVID19

 
Schematic representation of SARS-CoV-2-driven signaling pathways and potential drug targets (4)
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(1) Miguel Lourenço Varela et al. Acute Inflammation and Metabolism. Inflammation. (2018);41(4):1115-1127.
(2) Yu W, et al. Advances in T Cells Based on Inflammation in Metabolic Diseases. Cells. (2022)10;11(22):3554.
(3) Luis F García. Immune Response, Inflammation, and the Clinical Spectrum of COVID-19. Front Immunol. (2020);11:1441.
(4) Michele Catanzaro et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther. (2020);5(1):84.
(5) Ning Yuan et al. Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses. Transl Psychiatry. (2019);9(1):233.
(6) Estella A Newcombe et al. Inflammation: the link between comorbidities, genetics, and Alzheimer's disease. J Neuroinflammation. 2018;15(1):276.
(7) Christina H Liu et al. Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities. Nat Immunol. 2017;18(11):1175-1180.
(8) Peter Libby and Sebastian Kobold. Inflammation: a common contributor to cancer, aging, and cardiovascular diseases—expanding the concept of cardio-oncology. Cardiovasc Res. 2019;115(5): 824–829.
(9) Zarrin AA, et al. Kinase inhibition in autoimmunity and inflammation. Nat Rev Drug Discov. (2021);20(1):39-63.

  • Biomarker list

You can check the biomarker list included in this pathway, see below:

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