Cytokine profiling in patients with VCP-associated disease.

Abstract

Valosin containing protein (VCP) disease (also known as Inclusion Body Myopathy, Paget Disease of Bone and Frontotemporal Dementia [IBMPFD] syndrome) is caused by mutations in the gene encoding VCP classically affecting the muscle, bone and brain. Although the genetic cause has been identified, details regarding the pathogenesis of IBMPFD have not been fully determined. Muscle wasting observed in VCP disease is suggestive of cytokine imbalance. We hypothesized that dysfunctional protein homeostasis caused by VCP mutations leads to cytokine imbalances thereby contributing to the muscle wasting phenotype. Circulating levels of interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF a) and epidermal growth factor (EGF) were measured in plasma of patients with VCP disease or controls. TNF a and EGF were significantly altered in VCP disease as compared to control. TNF a was up-regulated, consistent with a cachexia phenotype and EGF levels were increased. No significant differences were observed in IL-4 and IL-6. Cytokine imbalances may be associated with VCP disease and may play a contributory role in VCP myopathy. Further understanding of how VCP dysfunction leads to aberrant protein homeostasis and subsequent cytokine imbalances may also aid in the understanding of other proteinopathies and in the development of novel treatments.

• Authors: Eric Dec, Prachi Rana, Veeral Katheria, Rachel Dec, Manaswitha Khare, Angèle Nalbandian, Szu-Yun Leu, Shlomit Radom-Aizik, Katrina Llewellyn, Lbachir BenMohamed, Frank Zaldivar, Virginia Kimonis
• Journal: Clinical and translational science (Clin Transl Sci) Vol. 7 Issue 1 Pg. 29-32 (Feb 2014) ISSN: 1752-8062 [Electronic] United States
• PMID: 24119107 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• Cell Cycle Proteins
• Cytokines
• IL4 protein, human
• IL6 protein, human
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-4
• Epidermal Growth Factor
• Adenosine Triphosphatases
• VCP protein, human
• Valosin Containing Protein

Topics

• Adenosine Triphosphatases (genetics)
• Case-Control Studies
• Cell Cycle Proteins (genetics)
• Cytokines (blood)
• Epidermal Growth Factor (blood)
• Frontotemporal Dementia (blood, etiology, genetics)
• Humans
• Interleukin-4 (blood)
• Interleukin-6 (blood)
• Muscle Development (genetics, physiology)
• Muscular Atrophy (blood, etiology, genetics)
• Muscular Dystrophies, Limb-Girdle (blood, etiology, genetics)
• Mutation
• Myositis, Inclusion Body (blood, etiology, genetics)
• Osteitis Deformans (blood, etiology, genetics)
• Signal Transduction
• Syndrome
• Tumor Necrosis Factor-alpha (blood)
• Valosin Containing Protein