Frontline: Inhibition of allergen-induced pulmonary inflammation by the tripeptide feG: a mimetic of a neuro-endocrine pathway.
Interactions between the neuro-endocrine system and immune system help maintain health. One interaction involves the superior cervical ganglia (SCG), which regulate the prohormone submandibular rat 1 (SMR1) produced by the submandibular gland (SMG). A peptide derived from SMR1, feG, has anti-inflammatory activity, and modification to D-isomer feG enhances bioactivity. We tested feG as a therapeutic agent for airways inflammation, using rats sensitized by OVA or Nippostrongylus brasiliensis (Nb). Treatment with feG but not fdG down-regulated OVA-challenge-induced increases in bronchoalveolar lavage (BAL)-derived macrophages, eosinophils and PMN (neutrophils) by 44%, 69% and 67%, respectively, at 24 h. We found that feG also reduced ICAM-1 on BAL-derived macrophages and eosinophils by 27% and 65%, and L-selectin on PMN by 55% following OVA challenge. Furthermore, feG but not fdG reduced the OVA-induced TNF increase in BAL fluid. We showed that feG also down-regulated both hyper-responsiveness to methacholine (by 27%) and microgranulomata formation in the lung parenchyma. In Nb-challenged rats, feG treatment inhibited ex vivo allergen-induced contraction of tracheal smooth muscle by up to 73%. In conclusion, feG, which is a mimetic of a peptide derived from a rat salivary gland prohormone, has anti-inflammatory properties in allergic airways inflammation in Brown-Norway rats. The role of the SCG-SMG neuro-endocrine pathway in allergic asthma and other inflammatory diseases requires additional study.
Dery
René E
RE
Department of Medicine, University of Alberta, Edmonton, Canada.
Ulanova
Marina
M
Puttagunta
Lakshmi
L
Stenton
Grant R
GR
James
Deborah
D
Merani
Shaheed
S
Mathison
Ronald
R
Davison
Joe
J
Befus
A Dean
AD
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN
D000485:Allergens; D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; C114891:tripeptide FEG