#interleukins

Patchy Signal

A skin condition characterised by scaly red patches, psoriasis is an autoimmune disorder linked to dysfunctional immune signalling, causing inflammation and accelerating cell division in the outermost layer of skin, the epidermis. Treatments targeting a shared feature of signalling proteins interleukin-12 (IL-12) and interleukin-23 (IL-23) can alleviate symptoms, but later drugs affecting only IL-23 proved even more effective, prompting questions about the role of IL-12. By selectively deleting the receptor for IL-12 in epidermal skin cells, keratinocytes, in mice, researchers showed that IL-12 actually protects against psoriasis. In the skin samples above, dividing keratinocytes in the epidermis (left of the white line), are highlighted in red; cells possessing the IL-12 receptor (left panel) are dividing less than those lacking it (right), suggesting that IL-12 acts to reduce cell proliferation. Future therapies should therefore concentrate on IL-23, a result with potential implications for other conditions treated by blocking both proteins.

Written by Emmanuelle Briolat

Image from work by Pascale Zwicky and colleagues, University of Zurich

Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Image copyright held by the original authors

Research published in Science Immunology, October 2021

Cell lines and culture conditions Human cancer cell lines of Raji (CCL-86), K562 (CCL-243), SKOV3 (HTB-77) and 293T (CRL-3216) were obtained from the American Type Culture Collection (ATCC). Raji cells were cultured in RPMI-1640 medium with 10% FBS, 2 mM l-glutamine (Invitrogen) and 1% penicillin–streptomycin (Invitrogen). SKOV3 and 293T cells were cultured in DMEM medium (Invitrogen)…

Authored by  Sheetal Verma

The primary target of influenza virus infection is the airway epithelial cells lining the respiratory mucosa but also infect alveolar macrophages and dendritic cells (DCs) that reside in the airways. In vitro as well as in vivo studies suggest that pro-inflammatory cytokines such as IL-1, TNF-α and IFN-β are secreted by infected cells and immune cells to sustain inflammatory response as well as induction of the chemokines (i.e. MCP-1, interferon-gamma (IFN-γ) which attract mononuclear leukocytes that occurs within two days of an influenza virus infection but most chemokines favour neutrophils.

https://juniperpublishers.com/aibm/AIBM.MS.ID.555556.php

Authored by  Sheetal Verma

The primary target of influenza virus infection is the airway epithelial cells lining the respiratory mucosa but also infect alveolar macrophages and dendritic cells (DCs) that reside in the airways. In vitro as well as in vivo studies suggest that pro-inflammatory cytokines such as IL-1, TNF-α and IFN-β are secreted by infected cells and immune cells to sustain inflammatory response as well as induction of the chemokines (i.e. MCP-1, interferon-gamma (IFN-γ) which attract mononuclear leukocytes that occurs within two days of an influenza virus infection but most chemokines favour neutrophils.

https://juniperpublishers.com/aibm/AIBM.MS.ID.555556.php

#Revision notes on #Interleukins and #Interferon

Interleukins are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cells (leukocytes).

  Interferons(IFNs) are a group of signaling proteins[1] made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. In a typical scenario, a virus-infected cell will…

A.  Cytokines and Growth Factors

     1.Hematopoiesis is regulated by a variety of cytokines and growth factors

        a. Most are secreted by cells of the bone marrow environment

            i. for example, macrophages, endothelial cells, fibroblasts, and adipocytes.

        b. Extracellular matrix of bone marrow can also be critical for binding cytokines to allow transactions with hematopoietic cells.

     2. Growth factors can act singly or synergistically.

        a. Synergistically means “acting together”

        b. Their effect on a particular cell type may be concentration dependent.

             i. Some can have an effect on multiple cell types

        c. Effects of hematopoietic growth factors are mediated by binding to specific receptors and activation of intracellular signaling pathways to promote cell proliferation or maturation.

     3. Some Important hematopoietic growth factors.

        a. Erythropoietin- stimulates growth and differentiation of erythroid and megakaryocytic progenitors.

        b. Thrombopoietin- stimulates production of megakaryocytes and platelets

        c. Interleukin 1 (IL-1)- induces expression of multiple cytokines, works with IL-3 (synergistic) in stimulating proliferation of hematopoietic progenitor cells, induces synthesis of acute phase reactants.

        d. Interleukin 2 (IL-2)- induces proliferation and activation of T cells, B cells, and NK cells

        e. Interleukin 3 (IL-3)- synergistic with lineage restricted factors to stimulate production and differentiation of macrophages, neutrophils, eosinophils, and basophils, supports proliferation of multipotential progenitor cells.

        f. Interleukin 4 (IL-4)- Diverse effects on T cells, monocytes, and granulocytes, synergistic with erythropoietin.

        g. Interleukin 5 (IL-5)- stimulates growth and differentiation of eosinophils,  chemotactic for eosinophils and activates eosinophil function.

        h. Interleukin  6 (IL-6)- stimulates hematopoietic progenitor cells, induces maturation of megakaryocytes and increases platelet number, induces production of acute phase reactants.

        i. Interleukin 8 (IL-6)- chemotactic activity for neutrophils, T cells, and basophils, activates release of lysosomal enzymes from neutrophils, induces adhesion of neutrophils to endothelial cells.

         j. Interleukin 9 (IL-9)- synergistic with erythropoietin to support development of erythroid burst-forming units.

         k. Interleukin 11 (IL-11)- synergistic with IL-3 to increases size, number, and ploidy of megakaryocytes.

             i. ploidy is number of chromosome sets, so DNA content increases in megakaryocytes

     4. Veterinary medicine has begun to use the effects of cytokines and growth factors to stimulate hematopoiesis in specific clinical situations.

        a. This means they can be used therapeutically for disease of hematopoietic stem cells

         b. Can be used to improve defense in animals with neutropenia (low number of neutrophils)

         c. Also can be used for defective neutrophil and macrophage function, immunodeficiency disease, and to stimulate hematopoiesis following chemotherapy.

     5. Some cats and dogs can develop antibodies against human cytokines or there can be restricted species activity for some cytokines.

Interleukins

The name (IL) followed by a number (for example IL-l or IL-2) was coined in an attempt to develop a standardized nomenclature for molecules secreted by, and acting on, leukocytes.

IL-1: It is an acute phase reactant synthesized by macrophages contributing to the acute inflammatory response, including fever, leukocyte recruitment, adhesion molecule activation, and stimulation of further chemokine production.

Mnemonic: One makes you burn like the sun.