BioMed Research International / 2010 / Article / Fig 2

Review Article

Molecular Modulation of Intestinal Epithelial Barrier: Contribution of Microbiota

Figure 2

A schematic illustration of the recognition of microbial associated molecular patterns (MAMPs), such as LPS (lipopolysaccharide), by pattern recognition receptors (PRRs) on epithelial cells and activation of three (A, B, and C) pathways that induce production of pro-inflammatory cytokines or chemokines. A. Expressed on the cell membrane of most intestinal epithelial cells (IECs), toll-like receptors (TLRs) are triggered by LPS. Four toll-like interleukin receptor (TIR) adaptors become involved in propagating TLR signaling, including Myd88 (myeloid differentiation primary-response gene 88), TIRAP (toll-interleukin-1 receptor domain containing adapter protein), TRAM (translocating chain-associated membrane protein), and the TRAF (TNF receptor associated factor) protein family. This interaction induces phosphorylation and activation of TAK1, leading to activation of IKKs. Inactive IKK sequesters NF ๐œ… B in the cytoplasm and leads to degradation of I ๐œ… B, with subsequent release of NF ๐œ… B that induces transcription of pro-inflammatory cytokines and chemokines. B. In various cells, Myd88-dependent signaling is associated with activations of TAK1, also known as MAP kinases. Extracellular signal-regulated kinase (MEK) is an intermediary of the MAPK pathway. Activated MEK subsequently phosphorylates ERK which translocates to the nucleus where it activates multiple transcription factors. Cytoplasmic nucleotide-binding oligomerization domain-like (NOD) receptors also recognize MAMP. The ligand NOD1 recognizes a peptidoglycan, a constituent only of gram-negative bacteria. NOD2 recognizes constituents of both gram-positive and gram-negative bacteria. NODs transduce signals in the pathway of NF ๐œ… B and MAP kinases.