A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse

Abstract

Highlights  A novel model to study lamellar signaling events during preferential weight bearing is presented.  Lamellar signaling events related to hypoxia and inflammation were assessed.  Lamellar hypoxia inducible factor-1a was increased in the supporting limb relative to the contralateral hind limb.  No differences in lamellar inflammatory signaling were present between the supporting limb and hind limbs.

Interleukin-17 pathway activation inEquus caballussupporting limb laminitis

“…It is possible that the differences in expression of IL-17 target genes among the severe acute samples reflects variation in a specific gene’s expression over time as the disease progresses, or as individual cells respond and adapt to receptor activation. There could also be an underlying genetic variability among horses, as suggested for “non-responders” to laminitis induction in experimental models [46; 48]. Additionally, we failed to detect significant expression of CCL20 (Fig 6), perhaps indicating a difference in an IL-17 pathway response due to species or tissue differences.…”

“…Models of SRL provide the most evidence for inflammation, either through upregulation of inflammatory mediators [15; 38; 39; 42-47] or leukocyte infiltration [50-52]. Recently, a model to mimic some aspects of SLL was reported [48]. Although this model did not result in clinical or histological laminitis and did not find upregulation of a similar set of inflammatory mediators identified in sepsis-related models, a relative increase in Hypoxia Inducible Factor (HIF)-1 α protein levels in the supporting limb suggests that ischemia may contribute to pathogenesis of SLL [48].…”

“…Recently, a model to mimic some aspects of SLL was reported [48]. Although this model did not result in clinical or histological laminitis and did not find upregulation of a similar set of inflammatory mediators identified in sepsis-related models, a relative increase in Hypoxia Inducible Factor (HIF)-1 α protein levels in the supporting limb suggests that ischemia may contribute to pathogenesis of SLL [48]. Interestingly, a mouse model of experimental autoimmune encephalitis (EAE) demonstrated that hypoxia is a metabolic cue that can serve as a “triggering event” mediated through HIF-1 α activation that initiates and perpetuates chronic inflammation and hypoxia through activation of IL-17 pathways that promote T h 17 differentiation and inhibit T reg differentiation [53].…”

Pain management for laminitis in the horse

“…There is a component of ongoing inflammation within both the lamellae and adjacent distal phalanx in chronic laminitis regardless of the inciting cause (Engiles et al 2015). Lamellar ischaemia may be an important initiator of supporting limb laminitis and may contribute to the progression of other forms of laminitis Gardner et al 2017). Ischaemia causes pain through local tissue lactic acidosis and the release of chemical mediators including serotonin, bradykinin, histamine, reactive oxygen species and adenosine (Benson et al 1999;Fu and Longhurst 2005).…”

“…; Gardner et al . ). Ischaemia causes pain through local tissue lactic acidosis and the release of chemical mediators including serotonin, bradykinin, histamine, reactive oxygen species and adenosine (Benson et al .…”