TNF-a, IL-1a, IL-6 and ICAM-1 Expression in Human Keratinocytes Stimulated in Vitro with Escherichia Coli Heat-Shock Proteins

Abstract

Bacterial heat-shock proteins (HSPs) from Escherichia co/i (GroES, GroEL and DnaK) were studied for their ability to induce by themselves the expression and release of tumour necrosis factor-a (TNF-a), interleukin-I a (IL-1 a), interleukin-6 (IL-6) and intercellular adhesion molecule-I (ICAM-1) by cultured human keratinocytes. The surface expression of ICAM-1 was also investigated. In the supernatants of untreated cells none or a minimal amount of these molecules was found. After 48 h of stimulation with GroEL significant amounts of TNF-a, IGIa, IL-6 and soluble ICAM-I were detected, reaching maximum concentrations at 1 pg ml-l. The same effect was elicited by DnaK but to a lesser extent. Treatment of keratinocytes with GroEL and DnaK also increased TNF-a, IL-la, IL-6 and ICAM-I mRNA levels. GroES showed significant activity only on the expression and release of IL-6. GroEL and DnaK were also able to up-regulate the surface expression of ICAM-1 on keratinocytes. The effects on ICAM-1 expression seemed to be directly due to HSPs and not mediated via cytokines. Furthermore, these effects were due to the properties of HSPs because they were inhibited by specific monoclonal antibodies. These findings support the potential role of HSPs in modulating cell interactions during immunological and inflammatory responses in the skin.

Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL

“…HSP60 (GroEL) and HSP70 (DnaK) have been shown to be required for virulence modulation (6,42), adherence (12,14,37), intracellular replication (25), invasion (44), and expression of TNF-␣ and adhesion molecules (15,30). Modulation of virulence by HSP100 family members, such as ClpB (8), ClpC (20,33,40), ClpE (34), ClpX (13), and ClpP (28,39), has also been documented.…”

Endocytosis of Mycobacterium tuberculosis Heat Shock Protein 60 Is Required to Induce Interleukin-10 Production in Macrophages*

“…However, upon interaction with TLR4, the Mtbhsp60 predominantly remained stranded on the cell surface and induced a dominant pro-inflammatorytype response characterized by higher TNF-␣ production. The Mtbhsp60 homologue of E. coli, Ecolihsp60, is known to induce predominantly a pro-inflammatory-type signaling (25,55,56). We found that Ecolihsp60 interacts with both the TLR2 and TLR4 to induce production of TNF-␣.…”

“…The E. coli homologue of Mtbhsp60, Ecolihsp60 (groEL), is known to induce predominantly a pro-inflammatory cytokine response in macrophages and human monocytes (25,55,56). We found that Ecolihsp60 can bind to both the TLR2 and TLR4 receptors on THP-1 macrophages (supplemental Fig.…”

Administration of heat shock protein 65 inhibits murine melanoma growth in vivo

“…However, extracellular HSP60 mediates immunological functions to induce a specific antitumor immune response that is able to reject the tumor (19). HSPs have remained almost unchanged throughout evolution, and greater than 50% of HSP65 is identical to HSP60 (19,(24)(25)(26)(27). Owing to this homology, antibodies elicited against HSP65 are able to cross-react with HSP60 (28).…”