Abstract
Introduction: Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects.Methods: Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell-dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum-transferred arthritis and in vitro cellular responses to NMU.Results: NMU-deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux.Conclusions: NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors.
Original language | English (US) |
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Article number | R29 |
Journal | Arthritis Research and Therapy |
Volume | 14 |
Issue number | 1 |
DOIs | |
State | Published - Feb 7 2012 |
Bibliographical note
Funding Information:We thank Pratik Patel and Donna Skinner for technical assistance. The studies were supported by an Arthritis Foundation Arthritis Investigator Award and a Minnesota Medical Foundation Research Grant (to BAB). BAB is also supported by K08 AR054317 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and by start-up funds from the University of Minnesota Department of Pediatrics. CB and DM’s participation was supported by R01 AR055271.