FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family.
Bronchoalveolar lavage fluid from mice with experimentally induced allergic pulmonary inflammation contains a novel 9.4 kDa cysteine-rich secreted protein, FIZZ1 (found in inflammatory zone). Murine (m) FIZZ1 is the founding member of a new gene family including two other murine genes expressed, respectively, in intestinal crypt epithelium and white adipose tissue, and two related human genes. In control mice, FIZZ1 mRNA and protein expression occur at low levels in a subset of bronchial epithelial cells and in non-neuronal cells adjacent to neurovascular bundles in the peribronchial stroma, and in the wall of the large and small bowel. During allergic pulmonary inflammation, mFIZZ1 expression markedly increases in hypertrophic, hyperplastic bronchial epithelium and appears in type II alveolar pneumocytes. In vitro, recombinant mFIZZ1 inhibits the nerve growth factor (NGF)-mediated survival of rat embryonic day 14 dorsal root ganglion (DRG) neurons and NGF-induced CGRP gene expression in adult rat DRG neurons. In vivo, FIZZ1 may modulate the function of neurons innervating the bronchial tree, thereby altering the local tissue response to allergic pulmonary inflammation.
Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
I N
IN
Holcomb
R C
RC
Kabakoff
B
B
Chan
T W
TW
Baker
A
A
Gurney
W
W
Henzel
C
C
Nelson
H B
HB
Lowman
B D
BD
Wright
N J
NJ
Skelton
G D
GD
Frantz
D B
DB
Tumas
F V
FV
Peale
D L
DL
Shelton
C C
CC
Hébert
D000595:Amino Acid Sequence; D000818:Animals; D001980:Bronchi / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002470:Cell Survival; D003545:Cysteine; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D020932:Nerve Growth Factor / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D012130:Respiratory Hypersensitivity / Q000235:genetics*; D020545:Respiratory Mucosa / Q000166:cytology; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C486574:RETNLB protein, human; C413576:Retnla protein, mouse; C486575:Retnla protein, rat; D020932:Nerve Growth Factor; D003545:Cysteine