Vitamin D, NOD2, autophagy and Crohn’s disease
By Linda on Dec 27, 2010 in F.I.G.H.T., Food | comments(0)
Excerpt:
Nod (nucleotide-binding oligomerization domain) 1 and Nod2 are intracellular PRMs (pattern-recognition molecules) of the NLR (Nod-like receptor) family. These proteins are implicated in the detection of bacterial peptidoglycan and regulate pro-inflammatory pathways in response to bacteria by inducing signalling pathways such as NF-kappaB (nuclear factor kappaB) and MAPKs (mitogen-activated protein kinases). The Nod proteins act independently of the TLR (Toll-like receptor) cascade, but potently synergize with the latter to trigger innate immune responses to microbes. Most importantly, mutations in Nod2 have been shown to confer susceptibility to several chronic inflammatory disorders, including Crohn’s disease, Blau syndrome and early-onset sarcoidosis, underscoring the role of Nod2 in inflammatory homoeostasis. This review summarizes the most recent findings in the field of Nod1 and Nod2 research.
Abstract
The innate immune system comprises several classes of pattern recognition receptors, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-1-like receptors (RLRs). TLRs recognize microbes on the cell surface and in endosomes, whereas NLRs and RLRs detect microbial components in the cytosol. Here we discuss the recent understanding in NLRs. Two NLRs, NOD1 and NOD2, sense the cytosolic presence of the peptidoglycan fragments meso-DAP and muramyl dipeptide, respectively, and drive the activation of mitogen-activated protein kinase (MAPK) and the transcription factor NF-kappaB. A different set of NLRs induces caspase-1 activation through the assembly of large protein complexes named inflammasomes. Genetic variations in several NLR members are associated with the development of inflammatory disorders. Further understanding of NLRs should provide new insights into the mechanisms of host defense and the pathogenesis of inflammatory diseases.
========================================
Curr Opin Immunol. 2008 Aug;20(4):377-82. Epub 2008 Jul 2.
NOD-like receptors (NLRs): bona fide intracellular microbial sensors.
Shaw MH, Reimer T, Kim YG, Nuñez G.
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Abstract
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) (nucleotide-binding domain leucine-rich repeat containing) family of proteins has been demonstrated to function as regulators of innate immune response against microbial pathogens. Stimulation of NOD1 and NOD2, two prototypic NLRs, results in the activation of MAPK and NF-kappaB. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of an inflammasome. This review discusses recent findings regarding the signaling pathways utilized by NLR proteins in the control of caspase-1 and NF-kappaB activation, as well as the nonredundant role of NLRs in pathogen clearance. The review also covers advances regarding the cellular localization of these proteins and the implications this may have on pathogen sensing and signal transduction.
========================================
Cell Host Microbe. 2008 Mar 13;3(3):146-57.
Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity.
LeBlanc PM, Yeretssian G, Rutherford N, Doiron K, Nadiri A, Zhu L, Green DR,Gruenheid S, Saleh M.
Department of Medicine, Division of Critical Care, and Centre for Study of Host Resistance, McGill University, Montreal H3A 1A1, Canada.
