Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial heat shock proteins (hsp) are evolutionary conserved immunodominant proteins that manifest amino acid homologies with hsp present in mammalian cells. Preimmunization with mycobacterial hsp65 has been found to protect against various forms of experimental arthritis. As these protective effects have previously been attributed to induction of self homologue cross-reactive T cell responses, the question was raised as to whether this protective effect could be extended to other highly conserved and immunodominant microbial Ags with mammalian homologues. Therefore, we immunized Lewis rats with conserved bacterial Ags (superoxide dismutase, aldolase, GAPDH, and hsp70). Although all Ags appeared highly immunogenic, we only found a protective effect in experimental arthritis after immunization with bacterial hsp70. The protective effect of hsp70 was accompanied with a switch in the subclasses of hsp70-specific Abs, suggesting the induction of Th2-like response. The most striking difference between immunization with hsp70 and all other immunodominant Ags was the expression of IL-10 found after immunization with hsp70. Even more, while immunization with hsp70 led to Ag-induced production of IL-10 and IL-4, immunization with aldolase led to increased production of IFN-gamma and TNF-alpha. Thus, the protective effect of conserved immunodominant proteins in experimental arthritis seems to be a specific feature of hsp. Therefore, hsp may offer unique possibilities for immunological intervention in inflammatory diseases.
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PMID:Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins. 1159 34

Adenosine released by cells in injurious or hypoxic environments has tissue-protecting and anti-inflammatory effects, which are also a result of modulation of macrophage functions, such as vascular endothelial growth factor (VEGF) production. As VEGF is a well-known target of hypoxia-inducible factor 1 (HIF-1), we hypothesized that adenosine may activate HIF-1 directly. Our studies using subtype-specific adenosine receptor agonists and antagonists showed that by activating the A(2A) receptor, adenosine treatment induced HIF-1 DNA-binding activity, nuclear accumulation, and transactivation capacity in J774A.1 mouse macrophages. Increased HIF-1 levels were also found in adenosine-treated mouse peritoneal macrophages. The HIF-1 activation induced by the A(2A) receptor-specific agonist CGS21680 required the PI-3K and protein kinase C pathways but was not mediated by changes in iron levels. Investigation of the molecular basis of HIF-1 activation revealed the involvement of transcriptional and to a larger extent, translational mechanisms. HIF-1 induction triggered the expression of HIF-1 target genes involved in cell survival (aldolase, phosphoglycerate kinase) and VEGF but did not induce inflammation-related genes regulated by HIF-1, such as TNF-alpha or CXCR4. Our results show that the formation of adenosine and induction of HIF-1, two events which occur in response to hypoxia, are linked directly and suggest that HIF-1 activation through A(2A) receptors may contribute to the anti-inflammatory and tissue-protecting activity of adenosine.
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PMID:Adenosine A2a receptor-mediated, normoxic induction of HIF-1 through PKC and PI-3K-dependent pathways in macrophages. 1750 24

The aim of the studies was to identify the regulatory mechanisms that act at different levels of the ongoing immune response in BALB/c mice infected with intestinal nematode H. polygyrus. The role of TGF-beta during the course of H. polygyrus infection and an immunosuppressive action of the nematode against eosinophil response in allergic pulmonary inflammation has been studied. An attempt to identify the immunoregulatory proteins of the parasite has been performed as well. The obtained results proved: (1) for the first time the direct role of TGF-beta in the regulation of the immune response during helminth infections. Neutralization of TGF-beta in vivo increased concentration of IL-12, TNF-alpha and IL-10 in serum of infected mice and restored the control number of eosinophils in the intestinal mucosa. The mobilization of the immune response after neutralization of TGF-beta led to persistent decrease of nematode egg production and faster rejection of the worm from mouse intestine; (2) for the first time it was shown that the reduction of eosinophil number was due to the lower production of eotaxin and reduced expression of CCR3 receptor, playing an essential role in the chemotaxis of these leukocytes in Ova-related asthma; (3) significant decrease of T cell proliferation by one of the H. polygyrus protein fraction. With the use of mass spectrometry seven proteins have been identified: two heat shock proteins, disulfide isomerase, calreticulin, calumenin, fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase. From the bibliographic data it may be supposed that calreticulin could mediate the downregulation of lymphocytes proliferation. The fraction with calreticulin stimulated also production of specific IgE.
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PMID:[Regulation of the immune response in BALb/c mice infected with Heligmosomoides polygyrus]. 1791 15