MECHANISMS OF INFLAMMATION AND ITS ASSOCIATEDPATHOGENESIS

1. MECHANISMS OF INFLAMMATION AND ITS ASSOCIATED
PATHOGENESIS
ROMANCE MANNA
M.Sc. Biotechnology
DEPARTMENT OF BIOTECHNOLOGY
MAULANA ABUL KALAM AZAD UNIVERSITY OF TECHNOLOGY

2. understanding about inflammation
• Biological protective response.
• Inducers of inflammation:-
PAMPs
 DAMPS
• Sensor (PRRs):-
Toll-like receptors (TLRs), nucleotide-binding oligomerization domain(Nod)-leucine-rich repeat-
containing receptors (NLRs), RIG like receptors, c –type lectin receptors
• TLRs -
Membrane-spanning protein
Macrophage, dendritic cells, B cell and non-immune cells like fibroblast and epithelial cells.
• NLRs -
cytoplasm bound PRR
 NLRP1, NLRP3 and NLRC4 , responsible for construction of inflammasome

3. INFLAMMATION Regulation Mediators
• TLR4 related inflammation-
type 1 transmembrane protein with single membrane spanning domain
 Adaptor protein MyD88, TIRAP and Pathways like MAPK
NF-κB ,AP-1 and IFN-1
• Inflammasome –
• NLRP3 mediated inflammation-
PYRIN (PYD) domain, nucleotide binding NACHT domain and leucinerich repeat (LRR) domain
cytosolic, multimeric protein, assembled by caspase-1.
 ASC adaptor protein, procaspase-1 and NLRP3
 IL-1β and IL-18 & gasdermin D
 PYROPTOSIS-proinflammatory programmed necrosis

4. • Figure: Mechanism of Inflammation

5. dysregulation of inflammation in human related disease
• Destructive role.
• Heart, pancreas, liver, kidney, lung, brain, intestinal tract, and reproductive
system, promote the tissue damage or disease
• Severe disease such as sepsis, cancer, diabetes, obesity, multiple sclerosis, gout,
atherosclerosis and autoimmune disease and also Addison's disease, bowel
disease etc.
• Acute inflammation
• Chronic inflammation.

6. example of disease
• ATHEROSCLEROSIS –
high saturated-fat diet, smoking, hypertension, hyperglycemia, obesity
VCAM1
 Monocyte to macrophage
Lesion and fatty streak
• RHEUMATOID ARTHrITIS :-
Synovial hyperplasia ,joint destruction
 exceed amount of endogenous DAMPs
 overproduction of IL-18

8. current status and future prospectus
•Drug designing
•Disease and specific molecular causative agent
•Identification of new therapeutic drugs
 VX740
MCC950
•Development of anti inflammatory therapy -diclofenac

9. conclusion
Though inflammation has destructive role, but is very necessary & essential for
immune system. All signaling pathway is not properly clear, but this little study
sets the stage for better understanding of inflammation in structural &
biochemical level. This mechanics might help various disease like RA, cancer,
CDC, diabetes etc. These basic idea may form basis of future research.

10. references
• Amin, M. N., Siddiqui, S. A., Hakim, L., Ahammed, S., & Kabir, A. (2020). Inflammatory cytokines in the pathogenesis of cardiovascular disease and cancer. https://doi.org/10.1177/2050312120965752
• Araki, Y., & Mimura, T. (2016). Inflammation in Rheumatoid Arthritis from the Perspective of the Epigenetic Landscape. Journal of Immunology Research, 2016.
• Barratt-due, A. (2012). Upstream versus downstream inhibition of Gram-negative induced inflammation. In Thesis, University of Oslo.
• Barton, G. M. (2008). A calculated response: Control of inflammation by the innate immune system. Journal of Clinical Investigation, 118(2), 413–420. https://doi.org/10.1172/JCI34431
• Barton, G. M., & Kagan, J. C. (2009). A cell biological view of toll-like receptor function: Regulation through compartmentalization. Nature Reviews Immunology, 9(8), 535–541. https://doi.org/10.1038/nri2587
• Bobryshev, Y. V., Ivanova, E. A., Chistiakov, D. A., Nikiforov, N. G., & Orekhov, A. N. (2016). Macrophages and Their Role in Atherosclerosis:Pathophysiology and Transcriptome Analysis. BioMed Research
International, 2016(Figure 1). https://doi.org/10.1155/2016/9582430
• Burdette, D. L., & Vance, R. E. (2013). STING and the innate immune response to nucleic acids in the cytosol. Nature Immunology, 14(1), 19–26. https://doi.org/10.1038/ni.2491.
• NLRP3 inflammasome in sepsis ,Xueyan Shi, Sichuang Tan, Sipin Tan May 13, 2021 https://doi.org/10.3892/mmr.2021.12153
• fig -2 https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.researchgate.net%2Ffigure%2FNLRP3-inflammasome-activation-during-type-II-diabetes-The-NLRP3-inflammasome-is-
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11. Thank you