Disease relevance of CYTL1

• These cytokine-like properties of MPO thus represent an additional dimension of the proinflammatory actions of MPO in vascular disease [1].
• Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro [2].
• In immune homeostasis, Cytl1 prevents the development of early-stage inflammatory arthritis and is associated with joint destruction but not with disease progression [3].
• Leptin is emerging as a cytokine-like immune regulator that has complex effects in both overnutrition and in the inflammatory response in malnutrition [4].
• These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine [5].
• Whereas traditionally, hypoxia was regarded mainly as an agent conferring resistance to radiation, there is now much evidence illustrating the cytokine-like properties of hypoxia as well as radiation [6].

High impact information on CYTL1

• CYTL1, originally cloned from CD34+ human bone marrow or cord blood mononuclear cells, was first identified to function as a potential autocrine/paracrine regulatory factor during mesenchymal cell chondrogenesis in vitro [7]. A study of CYTL1 knockout (CYTL1-/-) mice demonstrated that CYTL1 maintains cartilage homeostasis, and deletion of the CYTL1 gene results in deterioration of osteoarthritic cartilage [8].
• Recent study   shows that CYTL1 is highly expressed in the endometrium during the embryo implantation process and the CYTL1 expression pattern is regulated by ovarian hormones and that CYTL1 enhances endometrial proliferation, induces the secretion of endometrial LIF and HB-EGF, and even enhances endometrial cell adhesion to trophoblastic cells [3]. These indicate that CYTL1 is a potential molecular mediator of embryo implantation.
• In contrast to intracellular chaperones, chaperones present on the cell surface regulate the immune system and have cytokine-like effects [9].
• Although we did not identify increases in either interleukin-1 or TNF levels in bronchoalveolar lavage fluid, cytokines or a cytokine-like mechanism may mediate the syndrome of metal fume fever [10].
• We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro [11].
• In the thalamus, substantia nigra pars reticulata and hippocampus, an expression of proinflammatory cytokine like tumor necrosis factor-alpha and interleukin-1beta is induced [12].
• We propose that the evolutive cellular bases of stress are to be identified in immune cells, such as invertebrate hemocytes, producing a variety of cytokine-like molecules, capable at the same time of producing a variety of hormone- and neuropeptide-like molecules and of performing a proto-stress response (release of biogenic amines) [13].

Biological context of CYTL1

• Structurally Opn resembles a matrix protein yet it has well-characterized cytokine like properties including the regulation of cellular migration and cell-mediated immunity [14].
• It meets the criteria of having a cytokine-like function although its molecular structure does not show sequence homology with any of the vertebrate-type cytokines identified to date [15].
• We report the identification and characterization of a novel cytokine-like gene family using structure-based methods to search for novel four-helix-bundle cytokines in genomics databases [16].
• Thus, the so-called PBEF is not a cytokine-like secreted protein but an intracellular protein associated with the cell cycle [17].
• ADF/thioredoxin has several biologic functions, such as defense against cellular damage, activity to scavenge oxidative stress by hydrogen peroxide radicals and cytokine-like properties [18].

Anatomical context of CYTL1

• In contrast, the functions of the predominant secretory proteins of chromaffin cells, the chromogranins, are still largely unknown, but might include cytokine-like roles [19].
• Endothelial-monocyte activating polypeptide (EMAP)-II is a novel molecule with cytokine-like pro-inflammatory properties, inducing procoagulant activity on the surface of endothelial cells and monocyte/macrophages in vitro, as well as up-regulating E- and P-selectin expression [20].
• Chemokines are a superfamily of small cytokine-like proteins that induce, through their interaction with G protein-coupled receptors, cytoskeletal rearrangement, firm adhesion to endothelial cells, and directional migration [21].
• CP-64131 (CP), an aminobenzazepine with cytokine-like, physiologic effects similar to granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage (GM)-CSF, increases the number of neutrophils and stimulates marrow recovery after doxirubicin ablation [22].
• Osteopontin is an RGD-containing bone matrix protein with cytokine-like functions that is associated with early stages of Th1-mediated diseases [23].

Associations of CYTL1 with chemical compounds

• Dissecting the pathophysiologic role of endogenous lectins: Glycan-binding proteins with cytokine-like activity [24]?
• Thus, IL-8 appears to be an inhibitor of cytokine-like molecules that induce histamine release and may represent the previously described 8-kDa histamine release inhibitory factor present in mononuclear cell supernatants [25].
• In this test, mutant C60S was essentially inactive and mutant C57S was partly active, indicating together that at least some of the cytokine-like biological activities of MIF are dependent on the presence of cysteine 57 and 60 [26].
• Fungal exposure activates a series of serine proteases that process the protein Spaetzle to a cytokine-like form that acts as a ligand for Toll [27].
• Osteopontin (OPN) is a RGD-containing glycoprotein with cytokine-like, chemotactic, and pro-adhesive properties [28].

Physical interactions of CYTL1

• The TH subset cells interacted via short range cytokine-like factors, each cell type producing an autocrine factor and another factor which suppressed the development and proliferation of the other TH cell type [29].

Regulatory relationships of CYTL1

• The ovarian hormone-induced upregulation of Cytl1 production led to a significant increase in endometrial cell proliferation [3].
• Prolactin (PRL) enhances inflammatory and antitumor responses in vitro and thus exhibits Th1-type cytokine-like effects [30].
• Initial steps in leptin action include signalling through a cytokine-like receptor which activates the JAK/STAT pathway [31].

Other interactions of CYTL1

• Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes [32].
• Altogether, its expression and potential cytokine-like function in inflammation and in cancer suggests that S100A8/A9 may play a key role in inflammation-associated cancer [33].
• We conclude that CD163 has at least two distinct functions: the clearance of hemoglobin in its cell-bound form and participation in anti-inflammation as a soluble factor, exhibiting cytokine-like functions [34].
• These results provide new insights into proteolysis-independent cytokine-like effects of uPA [35].
• Based on its growth-promoting and cytokine-like properties, it is proposed that increased expression of TRX contributes to the disease activity in RA [36].

Analytical, diagnostic and therapeutic context of CYTL1

• Thus, immunostimulatory sequences can be identified within a pleiotropic cytokine like IL-1 and used in the rational design of novel vaccination strategies [37].
• Further clinical trials should concentrate on the combination of an early acting cytokine like IL-3 and later acting hemopoietic growth factors like erythropoietin and granulocyte colony-stimulating factor [38].

References