Welcome TO THE PRESENTATION ON INTERLEUKIN-6

INTERLEUKINE-6 ADVISED BY- Dr. A.H.M Khurshid Alam PREPARED BY- A.F.M. Towheedur Rahman(5325) Md. Saiful Islam(5302) Ashish Kumar Sharker(5321) Hazrat Ali(5309) Mst. Rejina Afrin(5320) Md. Ali Khan(5303) Md. Rashidul Hasan(5310) ADVISED BY- Dr. A.H.M Khurshid Alam

TOPICS INTRODUCTION PRINCIPAL SOURCES OF IL-6 STRUCTURE AND RECEPTOR CELL SIGNALING FOR IL-6 PRINCIPAL CELLULAR TARGETS BIOLOGICAL FUNCTIONS OF IL-6 TOXIC EFFECTS OF IL-6 REFERENCES THANKS GIVING

INTRODUCTION Interleukin-6(IL-6) is a protein that in human encoded by IL-6 gene. It is an interleukin that acts both as pro-inflammatory and anti- inflammatory cytokine. IL-6 is also a myokine (a cytokine that is produced by mast cell) that elevated in response to muscle contraction. It significantly elevated exercise and precedes the appearance of other cytokines in the circulation.

INTRODUCTION IL-6 is produced by many kinds of cells types including activated mono nuclear phagocytes, vascular endothelial cells and fibroblasts that function in both innate and adaptive immunity. It stimulates the synthesis of acute phase proteins by hepatocytes as well as the growth antibody producing B- lymphocytes.

Principal Sources of IL-6 IL-6 is mainly produced by: Mono nuclear phagocytes Vascular endothelial cells Fibroblasts T-cell and Other cells

STRUCTURE AND RECEPTOR The functional form of IL-6 is a homodimer with each subunit forming four α-helical globular domain. The size of IL-6 is 19KDa to 26KDA. The receptor for IL-6 consists of a cytokine binding protein (IL-6Rα chain known as CD126) and a signal transducing sub-unit (GP130) both of which belong to the type-1 cytokine binding receptor family. As IL-6 interacts with it’s receptor, it triggers the GP130 And IL-6R proteins to form a complex thus activating the receptor.

Figures of IL-6

Crystallographic Structure of IL-6

Cell Signaling For IL-6 The 130 KDa signal transducing sub-unit, GP-130 activates JAK-STATS signaling pathway, a signaling pathway initiated by cytokine binding to type-I and type-II cytokine receptors. This pathway sequentially involves activation of receptor associated Janus-Kinase(JAK) tyrosine kinases, JAK mediated tyrosine phosphorylation of the cytoplasmic tail of cytokine receptors, docking of signal transducers and activation of transcription (STATS) to the phosphorylated receptor chains. This phosphorylation causes dimerisation and nuclear translocation of STATS and STATS binding to the regulatory region of the target gene causing transcriptional activation of these genes.

Figure Of JAK-STATS Pathway

Principal Cellular Target Liver: Synthesis of acute phase proteins B-cells: Proliferation of antibody producing cells

Biological functions of IL-6 IL-6 has several diverse actions. These are stated as follows: In innate immunity, it stimulates the synthesis the synthesis of acute phase proteins by hepatocytes thus contributes to the systemic effect on inflammation. That’s why it is called acute phase response. In adaptive immunity, IL-6 stimulates the growth of B-lymphocytes that have differentiated into antibody producers.

Biological Functions of IL-6 It stimulates osteoclast formation. Thus is used to treat post- menopausal osteoporosis. IL-6 plays important role as an anti-inflammatory cytokine mediator through it’s inhibitory effect on TNF-α and IL-1. Il-6 is one of the most important mediators of fever. It is capable of crossing the BBB (blood brain barrier) and initiating the synthesis of prostaglandin in the hypothalamus. There by changing the body’s temperature set-point.

Biological Function of IL-6 IL-6 was shown to improve sleep-associated consolidation of emotional memories. It acts as a growth factor for neoplastic plasma cells (myelomas) and it also acts as autocrine growth factor. It stimulates BFU-Meg (burst forming unit megakarocyte) to increase platelet production.

Toxic effects of IL-6 Fever Abnormal liver function CNS toxicity Hypotension

REFERENCES Cellular And Molecular Immunology Abdul K. Abbas Anarew H. Lichtman Jordan S. Paber Medical Microbiology & Immunology- Warren Levison Ernest Tawetz Rang & Dale’s Pharmacology Microbiology Michael J. Pelczar Goodman & Gilman's- The Pharmacological Basis of Therapeutics. Internet

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