Kv1.3 channel‐blocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases

Autor: Vikas Dhawan, George K. Chandy, Satendra Chauhan, James D. Swarbrick, Shihchieh Jeff Chang, Mariel Gindin, Hai M. Nguyen, Luz M. Londono, Biswaranjan Mohanty, Rosendo Estrada, Sanjeev K. Upadhyay, Heike Wulff, Sandeep Chhabra, Mark R. Tanner, George A. Gutman, Jesus G. Valenzuela, Christine Beeton, Raymond S. Norton, Michael W. Pennington, Redwan Huq, Shawn P. Iadonato, Peter J. Hotez
Rok vydání: 2014
Předmět:
Models
Molecular
Male
Magnetic Resonance Spectroscopy
Protein Conformation
Physiology
T-Lymphocytes
Medical Physiology
Sequence Homology
C-C chemokine receptor type 7
medicine.disease_cause
Biochemistry
Brugia malayi
Research Communications
Mice
Models
Receptors
2.1 Biological and endogenous factors
Hypersensitivity
Delayed
Aetiology
Peptide sequence
Cells
Cultured
Phylogeny
Cultured
Kv1.3 Potassium Channel
Inbred Lew
biology
Effector
Delayed
probiotic worm therapy
Electrophysiology
Amino Acid
Infectious Diseases
Cytokines
Female
hookworm
Ancylostoma caninum
Biotechnology
Receptors
CCR7
Biochemistry & Molecular Biology
Cells
Molecular Sequence Data
T lymphocytes
Autoimmune Disease
Autoimmune Diseases
Structure-Activity Relationship
Cnidarian Venoms
Rare Diseases
Immune system
Clinical Research
Helminths
parasitic diseases
Hypersensitivity
Potassium Channel Blockers
Genetics
medicine
Animals
Humans
Amino Acid Sequence
Molecular Biology
Cell Proliferation
Ancylostoma ceylanicum
Sequence Homology
Amino Acid
Toxin
Molecular
ShK
Fibroblasts
biology.organism_classification
Peptide Fragments
Rats
Rats
Inbred Lew
Immunology
ion channel modulator
Biochemistry and Cell Biology
Immunologic Memory
CCR7
Zdroj: Chhabra, S; Chang, SC; Nguyen, HM; Huq, R; Tanner, MR; Londono, LM; et al.(2014). Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms: Implications for autoimmune diseases. FASEB Journal, 28(9), 3952-3964. doi: 10.1096/fj.14-251967. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/7263j9v0
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol 28, iss 9
ISSN: 1530-6860
0892-6638
Popis: © FASEB. The voltage-gated potassium (Kv) 1.3 channel is widely regarded as a therapeutic target for immunomodulation in autoimmune diseases. ShK-186, a selective inhibitor of Kv1.3 channels, ameliorates autoimmune diseases in rodent models, and human phase 1 trials of this agent in healthy volunteers have been completed. In this study, we identified and characterized a large family of Stichodactyla helianthus toxin (ShK)-related peptides in parasitic worms. Based on phylogenetic analysis, 2 worm peptides were selected for study: AcK1, a 51-residue peptide expressed in the anterior secretory glands of the dog-infecting hookworm Ancylostoma caninum and the human-infecting hookworm Ancylostoma ceylanicum, and BmK1, the C-terminal domain of a metalloprotease from the filarial worm Brugia malayi. These peptides in solution adopt helical structures closely resembling that of ShK. At doses in the nanomolar-micromolar range, they block native Kv1.3 in human T cells and cloned Kv1.3 stably expressed in L929 mouse fibroblasts. They preferentially suppress the proliferation of rat CCR7-effector memory T cells without affecting naive and central memory subsets and inhibit the delayed-type hypersensitivity (DTH) response caused by skin-homing effector memory T cells in rats. Further, they suppress IFNγ production by human T lymphocytes. ShK-related peptides in parasitic worms may contribute to the potential beneficial effects of probiotic parasitic worm therapy in human autoimmune diseases. - Chhabra, S., Chang, S. C., Nguyen, H. M., Huq, R., Tanner, M. R., Londono, L. M., Estrada, R., Dhawan, V., Chauhan, S., Upadhyay, S. K., Gindin, M., Hotez, P. J., Valenzuela, J. G., Mohanty, B., Swarbrick, J. D., Wulff, H., Iadonato, S. P., Gutman, G. A., Beeton, C., Pennington, M. W., Norton, R. S., Chandy, K. G. Kv1.3 channelblocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases.
Databáze: OpenAIRE
Externí odkaz: