The Developing Xenopus Limb as a Model for Studies on the Balance between Inflammation and Regeneration

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The roles of inflammation and immune cell reactivity triggered by amputation have only recently begun to be addressed in investigations of epimorphic regeneration, although studies of tissue repair in mammals clearly show the importance of the immune system in determining the quality of the repair process. Here, we first review inflammation-related work in non-mammalian systems of epimorphic regeneration which suggests that regeneration of an amputated appendage requires continuous modulation of the local immune response, from the first hours after amputation through the period of blastema patterning. We then present data on the effects of anti-inflammatory and proinflammatory agents on regeneration of larval Xenopus hindlimbs. Treatment with the glucocorticoid beclomethasone immediately after amputation inhibits regeneration in regeneration-complete stage 53 limbs. Other anti-inflammatory agents, including the inhibitors of cyclooxygenase-2 (COX-2) activity celecoxib and diclofenac, applied similarly to larvae amputated at stage 55, when the capacity for limb regeneration is normally being lost, restore regenerative capacity. This suggests that although injury-related events sensitive to glucocorticoids are necessary for regeneration, resolution of the inflammatory response may also be required to allow the complete regenerative response and normal blastema patterning. Conversely, if resolution of inflammation is prevented by local treatment of amputated limbs with beryllium, a strong immunoadjuvant, regeneration is inhibited, and gene expression data suggest that this inhibition results from a failure of normal blastema patterning. Both positive and negative effects of immune- or inflammation-related activities occur during anuran limb regeneration and this underscores the importance of considering immune cells in studies of epimorphic regeneration.

Original languageEnglish
Pages (from-to)1552-1561
Number of pages10
JournalAnatomical Record
Volume295
Issue number10
DOIs
StatePublished - Oct 2012

Fingerprint

Xenopus
limbs (animal)
limb
Regeneration
Extremities
regeneration
inflammation
amputation
Inflammation
glucocorticoids
beryllium
Amputation
anti-inflammatory agents
prostaglandin synthase
Celecoxib
tissue repair
anti-inflammatory activity
appendages
immune system
Glucocorticoids

Keywords

  • Annexins
  • Cell reprogramming
  • COX-2 inhibition
  • Glucocorticoid
  • Inflammation
  • Limb patterning
  • Limb regeneration
  • Xenopus

ASJC Scopus subject areas

  • Anatomy
  • Histology
  • Ecology, Evolution, Behavior and Systematics
  • Biotechnology

Cite this

The Developing Xenopus Limb as a Model for Studies on the Balance between Inflammation and Regeneration. / King, Michael; Neff, Anton W.; Mescher, Anthony.

In: Anatomical Record, Vol. 295, No. 10, 10.2012, p. 1552-1561.

Research output: Contribution to journalArticle

@article{096ddb5e9ea84fe78581cfb5831fd7f6,
title = "The Developing Xenopus Limb as a Model for Studies on the Balance between Inflammation and Regeneration",
abstract = "The roles of inflammation and immune cell reactivity triggered by amputation have only recently begun to be addressed in investigations of epimorphic regeneration, although studies of tissue repair in mammals clearly show the importance of the immune system in determining the quality of the repair process. Here, we first review inflammation-related work in non-mammalian systems of epimorphic regeneration which suggests that regeneration of an amputated appendage requires continuous modulation of the local immune response, from the first hours after amputation through the period of blastema patterning. We then present data on the effects of anti-inflammatory and proinflammatory agents on regeneration of larval Xenopus hindlimbs. Treatment with the glucocorticoid beclomethasone immediately after amputation inhibits regeneration in regeneration-complete stage 53 limbs. Other anti-inflammatory agents, including the inhibitors of cyclooxygenase-2 (COX-2) activity celecoxib and diclofenac, applied similarly to larvae amputated at stage 55, when the capacity for limb regeneration is normally being lost, restore regenerative capacity. This suggests that although injury-related events sensitive to glucocorticoids are necessary for regeneration, resolution of the inflammatory response may also be required to allow the complete regenerative response and normal blastema patterning. Conversely, if resolution of inflammation is prevented by local treatment of amputated limbs with beryllium, a strong immunoadjuvant, regeneration is inhibited, and gene expression data suggest that this inhibition results from a failure of normal blastema patterning. Both positive and negative effects of immune- or inflammation-related activities occur during anuran limb regeneration and this underscores the importance of considering immune cells in studies of epimorphic regeneration.",
keywords = "Annexins, Cell reprogramming, COX-2 inhibition, Glucocorticoid, Inflammation, Limb patterning, Limb regeneration, Xenopus",
author = "Michael King and Neff, {Anton W.} and Anthony Mescher",
year = "2012",
month = "10",
doi = "10.1002/ar.22443",
language = "English",
volume = "295",
pages = "1552--1561",
journal = "Anatomical Record",
issn = "1932-8486",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - The Developing Xenopus Limb as a Model for Studies on the Balance between Inflammation and Regeneration

AU - King, Michael

AU - Neff, Anton W.

AU - Mescher, Anthony

PY - 2012/10

Y1 - 2012/10

N2 - The roles of inflammation and immune cell reactivity triggered by amputation have only recently begun to be addressed in investigations of epimorphic regeneration, although studies of tissue repair in mammals clearly show the importance of the immune system in determining the quality of the repair process. Here, we first review inflammation-related work in non-mammalian systems of epimorphic regeneration which suggests that regeneration of an amputated appendage requires continuous modulation of the local immune response, from the first hours after amputation through the period of blastema patterning. We then present data on the effects of anti-inflammatory and proinflammatory agents on regeneration of larval Xenopus hindlimbs. Treatment with the glucocorticoid beclomethasone immediately after amputation inhibits regeneration in regeneration-complete stage 53 limbs. Other anti-inflammatory agents, including the inhibitors of cyclooxygenase-2 (COX-2) activity celecoxib and diclofenac, applied similarly to larvae amputated at stage 55, when the capacity for limb regeneration is normally being lost, restore regenerative capacity. This suggests that although injury-related events sensitive to glucocorticoids are necessary for regeneration, resolution of the inflammatory response may also be required to allow the complete regenerative response and normal blastema patterning. Conversely, if resolution of inflammation is prevented by local treatment of amputated limbs with beryllium, a strong immunoadjuvant, regeneration is inhibited, and gene expression data suggest that this inhibition results from a failure of normal blastema patterning. Both positive and negative effects of immune- or inflammation-related activities occur during anuran limb regeneration and this underscores the importance of considering immune cells in studies of epimorphic regeneration.

AB - The roles of inflammation and immune cell reactivity triggered by amputation have only recently begun to be addressed in investigations of epimorphic regeneration, although studies of tissue repair in mammals clearly show the importance of the immune system in determining the quality of the repair process. Here, we first review inflammation-related work in non-mammalian systems of epimorphic regeneration which suggests that regeneration of an amputated appendage requires continuous modulation of the local immune response, from the first hours after amputation through the period of blastema patterning. We then present data on the effects of anti-inflammatory and proinflammatory agents on regeneration of larval Xenopus hindlimbs. Treatment with the glucocorticoid beclomethasone immediately after amputation inhibits regeneration in regeneration-complete stage 53 limbs. Other anti-inflammatory agents, including the inhibitors of cyclooxygenase-2 (COX-2) activity celecoxib and diclofenac, applied similarly to larvae amputated at stage 55, when the capacity for limb regeneration is normally being lost, restore regenerative capacity. This suggests that although injury-related events sensitive to glucocorticoids are necessary for regeneration, resolution of the inflammatory response may also be required to allow the complete regenerative response and normal blastema patterning. Conversely, if resolution of inflammation is prevented by local treatment of amputated limbs with beryllium, a strong immunoadjuvant, regeneration is inhibited, and gene expression data suggest that this inhibition results from a failure of normal blastema patterning. Both positive and negative effects of immune- or inflammation-related activities occur during anuran limb regeneration and this underscores the importance of considering immune cells in studies of epimorphic regeneration.

KW - Annexins

KW - Cell reprogramming

KW - COX-2 inhibition

KW - Glucocorticoid

KW - Inflammation

KW - Limb patterning

KW - Limb regeneration

KW - Xenopus

UR - http://www.scopus.com/inward/record.url?scp=84866159146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866159146&partnerID=8YFLogxK

U2 - 10.1002/ar.22443

DO - 10.1002/ar.22443

M3 - Article

C2 - 22933418

AN - SCOPUS:84866159146

VL - 295

SP - 1552

EP - 1561

JO - Anatomical Record

JF - Anatomical Record

SN - 1932-8486

IS - 10

ER -