title: Cross talk between neuroregulatory molecule and monocyte: nerve growth factor activates the inflammasome.
abstract: BACKGROUND
  Increasing evidence points to a role for the extra-neuronal nerve growth factor (NGF) in acquired immune responses. However, very little information is available about its role and underlying mechanism in innate immunity. The role of innate immunity in autoimmune diseases is becoming increasingly important. In this study, we explored the contribution of pleiotropic NGF in the innate immune response along with its underlying molecular mechanism with respect to IL-1β secretion.
  
  
  METHODS
  Human monocytes, null and NLRP3 deficient THP-1 cell lines were used for this purpose. We determined the effect of NGF on secretion of IL-1β at the protein and mRNA levels. To determine the underlying molecular mechanism, the effect of NGF on NLRP1/NLRP3 inflammasomes and its downstream key protein, activated caspase-1, were evaluated by ELISA, immunoflorescence, flow cytometry, and real-time PCR.
  
  
  RESULTS
  In human monocytes and null THP-1 cell line, NGF significantly upregulates IL-1β at protein and mRNA levels in a caspase-1 dependent manner through its receptor, TrkA. Furthermore, we observed that NGF induces caspase-1 activation through NLRP1/NLRP3 inflammasomes, and it is dependent on the master transcription factor, NF-κB.
  
  
  CONCLUSIONS
  To best of our knowledge, this is the first report shedding light on the mechanistic aspect of a neuroregulatory molecule, NGF, in innate immune response, and thus enriches our understanding regarding its pathogenic role in inflammation. These observations add further evidence in favor of anti-NGF therapy in autoimmune diseases and also unlock a new area of research about the role of NGF in IL-1β mediated diseases.
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Davis, CA, 95616, United States of America; VA Medical Center Sacramento, Mather, CA, 95655, United States of America.
authors: Ananya
authors: A
authors: Datta-Mitra
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Davis, CA, 95616, United States of America; VA Medical Center Sacramento, Mather, CA, 95655, United States of America.
authors: Smriti
authors: S
authors: Kundu-Raychaudhuri
authors: VA Medical Center Sacramento, Mather, CA, 95655, United States of America; Department of Dermatology, University of California Davis, School of Medicine, Sacramento, CA, 95817, United States of America.
authors: Anupam
authors: A
authors: Mitra
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Davis, CA, 95616, United States of America; VA Medical Center Sacramento, Mather, CA, 95655, United States of America.
authors: Siba P
authors: SP
authors: Raychaudhuri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; D020932:Nerve Growth Factor / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D016328:NF-kappa B; C502240:NGF protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C453881:NLRP3 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D020932:Nerve Growth Factor; D020170:Caspase 1