Expression of interleukin-17B in mouse embryonic limb buds and regulation by BMP-7 and bFGF

doi:10.1016/j.bbrc.2004.11.087

Biochemical and Biophysical Research Communications

Volume 326, Issue 3, 21 January 2005, Pages 624-631

https://doi.org/10.1016/j.bbrc.2004.11.087 Get rights and content

Abstract

Interleukin-17B (IL-17B) is a member of interleukin-17 family that displays a variety of proinflammatory and immune modulatory activities. In this study, we found that IL-17B mRNA was maximally expressed in the limb buds of 14.5 days post coitus (dpc) mouse embryo and declined to low level at 19.5 dpc. By immunohistochemical staining, the strongest IL-17B signals were observed in the cells of the bone collar in the primary ossification center. The chondrocytes in the resting and proliferative zones were stained moderately, while little staining was seen in the hypertrophic zone. Furthermore, in both C3H10T1/2 and MC3T3-E1 cells, the IL-17B mRNA was up-regulated by recombinant human bone morphogenetic protein-7, but down-regulated by basic fibroblast growth factor via the extracellular signal-regulated kinase pathway. This study provides the first evidence that IL-17B is expressed in the mouse embryonic limb buds and may play a role in chondrogenesis and osteogenesis.

Section snippets

Materials and methods

Mouse embryos and neonatal mice. This study was approved by the Institutional Animal Care and Use Committee of the University of California, Davis, according to National Institutes of Health guidelines. Timed pregnant CD-1 mice were obtained from the Charles River Laboratories (Wilmington, MA) and kept at the animal facilities of University of California, Davis. The pregnant mice from 9.5 to 17.5 dpc and neonatal mice born at 19.5 dpc were euthanized by CO₂ asphyxiation. Embryos and neonatal mice

IL-17B mRNA was expressed in mouse embryonic limb buds

IL-17 cytokines form a unique novel family, of which the prototype member IL-17A has been studied extensively [1], [2], [3], [4], [5], [6]. However, reports on IL-17B were very limited [10], [11], [12], [21]. Our finding that IL-17B was expressed in calf articular cartilage but not in adult cow cartilage led us to hypothesize that IL-17B is perhaps predominantly expressed in early stages of bone development. To test our hypothesis, we isolated total RNA from mouse embryonic limb buds and limbs

Acknowledgments

We thank Dr. T.K. Sampath, Creative BioMolecules, Hopkinton, MA, for his generous gift of BMP-7. This study was supported by a grant from the National Institutes of Health (5R01AR047345-02).

References (32)

T.A. Moseley et al.
Interleukin-17 family and IL-17 receptors
Cytokine Growth Factor Rev.
(2003)
P. Miossec
IL-17 in rheumatoid arthritis: a new target for treatment or just another cytokine?
Joint Bone Spine
(2004)
J.K. Kolls et al.
Interleukin-17 family members and inflammation
Immunity
(2004)
Z. Yao et al.
Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor
Immunity
(1995)
Y. Shi et al.
A novel cytokine receptor–ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity
J. Biol. Chem.
(2000)
J. Lee et al.
IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1
J. Biol. Chem.
(2001)
X. Yang et al.
Sef interacts with TAK1 and mediates JNK activation and apoptosis
J. Biol. Chem.
(2004)
S. Xiong et al.
hSef inhibits PC-12 cell differentiation by interfering with Ras-mitogen-activated protein kinase MAPK signaling
J. Biol. Chem.
(2003)
R.B. Yang et al.
A novel interleukin-17 receptor-like protein identified in human umbilical vein endothelial cells antagonizes basic fibroblast growth factor-induced signaling
J. Biol. Chem.
(2003)
D. Kovalenko et al.
Sef inhibits fibroblast growth factor signaling by inhibiting FGFR1 tyrosine phosphorylation and subsequent ERK activation
J. Biol. Chem.
(2003)

E.E. Moore et al.

Expression of IL-17B in neurons and evaluation of its possible role in the chromosome 5q-linked form of Charcot-Marie-Tooth disease

Neuromuscul. Disord.

(2002)

Z. You et al.

c-Myc sensitizes cells to tumor necrosis factor-mediated apoptosis by inhibiting nuclear factor kappa B transactivation

J. Biol. Chem.

(2002)

J. Laurikkala et al.

Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot

Dev. Biol.

(2003)

P.J. Marie

Fibroblast growth factor signaling controlling osteoblast differentiation

Gene

(2003)

J. Witowski et al.

Interleukin-17: a mediator of inflammatory responses

Cell. Mol. Life Sci.

(2004)

L.K. Stamp et al.

Interleukin-17: the missing link between T-cell accumulation and effector cell actions in rheumatoid arthritis?

Immunol. Cell Biol.

(2004)

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^☆: Abbreviations: IL-17, interleukin-17; BMP-7, bone morphogenetic protein-7; bFGF, basic fibroblast growth factor; ERK, extracellular signal-regulated kinase; Sef, similar expression to fgf genes; PTHrP, parathyroid hormone-related protein.

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Expression of interleukin-17B in mouse embryonic limb buds and regulation by BMP-7 and bFGF☆

Abstract

Section snippets

Materials and methods

IL-17B mRNA was expressed in mouse embryonic limb buds

Acknowledgments

Cytokine Growth Factor Rev.

Joint Bone Spine

Immunity

Immunity

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Neuromuscul. Disord.

J. Biol. Chem.

Dev. Biol.

Gene

Interleukin-17: a mediator of inflammatory responses

Cell. Mol. Life Sci.

Interleukin-17: the missing link between T-cell accumulation and effector cell actions in rheumatoid arthritis?

Immunol. Cell Biol.