Extracellular Cyclophilins Contribute to the Regulation of Inflammatory Responses

Abstract

The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

“…It is known that macrophages express Bsg, and that Bsg could be a ligand for E-selectin. 27,34 We also confirmed that Bsg on THP-1, the human monocytic cell line, bound to E-selectin (data not shown). Consider- ing that E-selectin expression was induced to similar degrees in both genotypes, it is likely that the difference in macrophage infiltration between Bsg ϩ/ϩ and Bsg Ϫ/Ϫ mice is due to the presence of Bsg on macrophages.…”

Identity and transfer of male reproductive gland proteins of the dengue vector mosquito, Aedes aegypti: Potential tools for control of female feeding and reproduction

“…AAEL011758 and AAEL013279 are predicted cyclophilins. The involvement of cyclophilins in immune response has been documented in D. melanogaster (Guedes et al, 2005) and mammals (Arora et al, 2005;Barik, 2006) and has been proposed in Xenopus laevis, where a cyclophilin is found in skin secretions (Miele et al, 2003).…”

Molecular cloning and characterization of two isoforms of cyclophilin A gene from Venerupis philippinarum

“…For example, CypAeCsA complex can bind and inhibit calcineurin in T-lymphocytes, which blocks the T cell signal transduction to achieve immunosuppression [19]. Although CypA was originally believed to exist solely as an intracellular protein, later studies have revealed that it can be secreted by cells in response to inflammatory stimuli [20]. The clinical importance of Cyps has been implicated in diverse pathological conditions, such as HIV [21], hepatitis B and C viral infection [22], atherosclerosis [23], vascular diseases [24] and Rheumatoid Arthritis pathogenesis [25].…”