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R M Medzhitov

Publications and source records attributed to R M Medzhitov.

8 recordsLinked to original sources
PubMed2001

An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells.

Tissue damage induced by infection or injury can result in necrosis, a mode of cell death characterized by induction of an inflammatory response. In contrast, cells dying by apoptosis do not induce inflammation. However, the reasons for underlying differences between these two modes of cell death in inducing inflammation are not known. Here we show that necrotic cells, but not apoptotic cells, activate NF-kappaB and induce expression of genes involved in inflammatory and tissue-repair responses, including neutrophil-specific chemokine genes KC and macrophage-inflammatory protein-2, in viable fibroblasts and macrophages. Intriguingly, NF-kappaB activation by necrotic cells was dependent on Toll-like receptor 2, a signaling pathway that induces inflammation in response to microbial agents. These results have identified a novel mechanism by which cell necrosis, but not apoptosis, can induce expression of genes involved in inflammation and tissue-repair responses. Furthermore, these results also demonstrate that the NF-kappaB/Toll-like receptor 2 pathway can be activated both by exogenous microbial agents and endogenous inflammatory stimuli.

Animals↗
PubMed1998

Subtle conformational changes induced in major histocompatibility complex class II molecules by binding peptides.

Intracellular trafficking of major histocompatibility complex (MHC) class II molecules is characterized by passage through specialized endocytic compartment(s) where antigenic peptides replace invariant chain fragments in the presence of the DM protein. These changes are accompanied by structural transitions of the MHC molecules that can be visualized by formation of compact SDS-resistant dimers, by changes in binding of mAbs, and by changes in T cell responses. We have observed that a mAb (25-9-17) that is capable of staining I-Ab on the surface of normal B cells failed to interact with I-Ab complexes with a peptide derived from the Ealpha chain of the I-E molecule but bound a similar covalent complex of I-Ab with the class II binding fragment (class II-associated invariant chain peptides) of the invariant chain. Moreover, 25-9-17 blocked activation of several I-Ab-reactive T cell hybridomas but failed to block others, suggesting that numerous I-Ab-peptide complexes acquire the 25-9-17(+) or 25-9-17(-) conformation. Alloreactive T cells were also able to discriminate peptide-dependent variants of MHC class II molecules. Thus, peptides impose subtle structural transitions upon MHC class II molecules that affect T cell recognition and may thus be critical for T cell selection and autiommunity.

Amino Acid Sequence↗
PubMed1992

[The role of ATPase activity in the function of molecular chaperones and some regulatory proteins].

It has been suggested that the ATPase activity of molecular chaperones depends on the structure of the recognizable determinant in the target protein. The role of molecular chaperones in polypeptide chain folding and protein association into oligomeric complexes is discussed. The putative regulatory role of the determinant ATPase activity of molecular chaperones and those of some regulatory proteins are discussed. A hypothesis is proposed that determinant ATPases play a part in the increasing specificity of intermacromolecular interactions.

Adenosine Triphosphatases↗
PubMed1991

[Evolution of regulatory proteins].

A concept of the evolution of signal molecules and their receptors is proposed. The formation of novel regulatory proteins by way of gene fusion and gene shuffling and the role of these processes in metabolic integration are considered. The different receptor variants may be due to alternative splicing which is regulated in a tissue-specific manner.

Biological Evolution↗