Leukocyte integrin α4β7 associates with heat shock protein 70

Abstract

The leukocyte integrin cell adhesion molecules α4β7 and αEβ7 mediate the homing and retention of lymphocytes to the gut, and sites of inflammation. Here we have identified heat shock protein 70 (HSP70) as a major protein that associates with the cytoplasmic domain of the integrin β7 subunit. HSPs are molecular chaperones that protect cells from stress but more recently have been reported to also regulate cell adhesion and invasion via modulation of β1, β2, and β3 integrins and integrin-associated signalling molecules. Several HSP70 isoforms including HSP70-3, HSP70-1L, HSP70-8, and HSP70-9 were specifically precipitated from T cells by a bead-conjugated β7 subunit cytoplasmic domain peptide and subsequently identified by high-resolution liquid chromatography-tandem mass spectrometry. In confirmation, the β7 subunit was co-immunoprecipitated from a T cell lysate by an anti-HSP70 antibody. Further, recombinant human HSP70-1a was precipitated by β7 cytoplasmic domain-coupled beads. The HSP70 inhibitor KNK437 decreased the expression of HSP70 without affecting the expression of the β7 integrin. It significantly inhibited α4β7-mediated adhesion of T cells to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), suggesting HSP70 is critical for maintaining β7 integrin signalling function. The functional implications of the association of β7 integrins with the different isoforms of HSP70 warrants further investigation.

Hyperelastic, shape‐memorable, and ultra‐cell‐adhesive degradable polycaprolactone‐polyurethane copolymer for tissue regeneration

“…Similar fibronectin adsorption amounts and supraphysiologically high stiffness (30–50 MPa) than pre‐mineralized extracellular matrix were detected in ISB‐P and PCL (Figure S14), reinforcing the involvement of biological factors, here Hsp1a‐induced integrin α5 and αν functional activity, in enhancing stem cell adhesion on ISB‐P 86 . Taken together, these results revealed that the integrin α5 and αν subunit functions as major surface receptors for ISB‐P in stem cells possibly by the activation of Hspa1a in a special biological signaling pathway, 87–89 not by physical factors such as surface roughness and adhesive protein adsorption. Further study is necessary to investigate whether the activation of Hspa1a genes by ISB‐P to regulate cell adhesion is unique among PU‐PCL shape‐memory polymers and what are the key chemical structures to tune Hspa1a genes.…”

Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation

“…Extracellular Hsp70 binds Toll-like receptors and other surface receptors on neighboring macrophages, monocytes, neutrophils, or dendritic cells, which initiates an inflammatory response through activation of the NFB and MAP kinase pathways (1,3,4,13,23,50). A hypothetical role for extracellular Hsp70 activity is also supported by work in other cell models showing that Hsp70 associates with integrins (12), that the Hsp70 family member Grp78/binding immunoglobulin protein and PDI cooperate to carry out chaperone activities (17), and that the cytosolic Hsp70 member Hsc70 associates with PDI and ERp57 in endothelial cell lipid rafts to facilitate integrin activation (17,42).…”

Calcium Phosphate Bone Cements Incorporated with Black Phosphorus Nanosheets Enhanced Osteogenesis

“…According to previous reports, 46 osteoblasts, stimulated by temperature, show heat shock response as well as upregulation of heat shock proteins, which activates the ERK-Wnt/β-catenin signaling pathway as well as downstream MMP-2 expression to promote osteogenic differentiation. 47,48 In addition, under certain limited conditions, certain heat can sterilize to avoid bacterial infection during bone repair. In summary, the benefits of the photothermal properties of bone cement on bone healing mainly include the following three aspects: First, promotion of the expression of heat shock proteins and then activation of corresponding signal pathways to promote bone induction.…”