Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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GRO3; GRO-gamma(1-73); Growth-regulated protein gamma; MGSA (= melanoma growth-stimulating activity)

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Anisowicz A et al (1987)

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Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure (see below chemokines).

In the CC-chemokines the cysteines follow each other directly, in the CXC-chemokines (see figure) they are separated by 1, in the CXXXC-chemokines by 3 other amino acids. Chemokines are produced and secreted by a multitude of immune cells. They mediate their signals by means of specific chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the development and homeostasis of tissues.

Increased chemokine expressions are found in chronic inflammatory diseases such as HIV infection, atopic eczema, bronchial asthma, allergic rhinitis and psoriasis vulgaris. Chemokines play a positive role e.g. in wound healing, haematopoiesis (blood formation) or the defence against infections. The fact that chemokine receptors are not only present on inflammatory cells but also on tumor cells and endothelial cells suggests that they are also involved in the migration of tumor cells or the metastatic behavior of various tumors.

CXCL3, also called "chemokines (C-X-C motif) ligand 3", is a small cytokine belonging to the CXC chemokine family, which influences the migration and adhesion of monocytes but also of neutrophil granulocytes. Originally it could be shown that a protein called MGSA (= melanoma growth-stimulating activity) is identical to CXCL3. The gene coding for CXCL3 is located on chromosome 4q12-q13, in close proximity to other CXC chemokines. CXCL3 binds to the surface receptor CXCR2, which also performs independent functions.

General information
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CXCL3 recruits neutrophil granulocytes. The chemokine is involved in various inflammatory and neoplastic processes.

Human intestinal mast cells express numerous chemokines. Besides CCL3 these are: CCL1, CCL2, CCL4, CCL5, CCL7, CCL18, CCL20, CXCL2, CXCL3, CXCL8 and XCL1. The expression of CXCL3 could be massively inhibited by Interleukin-4.

Keratinocytes express interleukin-17A-triggered chemokines such as CCL20, CXCL1, CXCL5, CXCL6 and CXCL8 in addition to CXCL3 to attract myeloid dendritic cells, Th17 cells and neutrophil granulocytes during psoriatic inflammation.

CXCL3 and its receptor are significantly overexpressed in (among other cytokines such as: interleukin-6 and -8, ATF3, CXCL2) pleural mesothelial cells and play a role in the inflammation of asbestosis.

CXCL3, its CXCL3 chemokine receptor and CXCL13 are clearly expressed in mature adipocytes. Suppression of CXCL3 inhibits fat tissue differentiation.

CXCL3 is expressed by specific cerebellar granule neuron precursors. If there is a depression of CXCL3 expression in these precursors, the frequency of medulloblastomas increases.

CXCL3 and its receptor CXCR2 are expressed or overexpressed in prostate epithelia and prostate carcinoma cells and appear to play an important role in the development of prostate carcinoma. This chemokine is also important for the pathogenesis of breast cancer and melanoma and other malignancies.

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Last updated on: 29.10.2020