bioRxiv Science⌕ Search

Biology subjects

Little, C.

Publications and source records attributed to Little, C..

2 recordsLinked to original sources

Proresolving mediators LXB4 and RvE1 regulate inflammation in stromal cells from patients with shoulder tendon tears

Tendon stromal cells isolated from patients with chronic shoulder rotator-cuff tendon tears show dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation, therefore new therapeutic approaches targeting tendon stromal cells are required. We determined if two specialised pro-resolving mediators (SPM) LXB4 and RvE1, modulated the bioactive lipid mediator (LM) profiles of IL-1{beta} stimulated tendon cells derived from patients with shoulder tendon tears and healthy volunteers. We also determined if LXB4/RvE1 treatments moderated the pro-inflammatory phenotype of tendon tear stromal cells. Incubation of IL-1{beta} treated patient derived tendon cells in LXB4/RvE1 upregulated concentrations of SPM. RvE1 treatment specifically increased 15-epi-LXB4 and regulated PGF2. LXB4 or RvE1 also induced expression of the SPM biosynthetic enzymes 12-liopxygeanse (ALOX12), and ALOX15. RvE1 treatment upregulated proresolving receptor ERV1 compared to vehicle treated cells. Incubation in LXB4 or RvE1 moderated the proinflammatory phenotype of patient derived tendon tear cells, regulating markers of tendon inflammation, including Podoplanin, CD90, STAT-1 and IL-6. These treatments also suppressed JNK1/2/3, Lyn, STAT-3 and STAT-6 and induced p70s6kinase phospho-kinase signalling. LXB4 and RvE1 counter-regulate inflammatory processes in tendon stromal cells, supporting the role of these molecules as potential therapeutics to resolve tendon inflammation.

cell biology↗

Upstream trophic structure modulates downstream community dynamics via resource subsidies.

In many natural systems, the physical structure of the landscape dictates the flow of resources. Despite mounting evidence that communities dynamics can be indirectly coupled by reciprocal among-ecosystem resource flows, our understanding of how directional resource flows might indirectly link biological communities is limited. We here propose that differences in community structure upstream should lead to different downstream dynamics, even in the absence of dispersal. We report an experimental test of the effect of upstream community structure on downstream community dynamics in a simplified but highly controlled setting, using protist microcosms. We implemented directional flows of resources, without dispersal, from a standard resource pool into upstream communities of contrasting interaction structure and then to further downstream communities of either one or two trophic levels. Our results demonstrate that different types of species interactions in upstream habitats may lead to different population sizes and levels of biomass in these upstream habitats. This, in turn, leads to varying levels of detritus transfer (dead biomass) to the downstream communities, thus influencing their population densities and trophic interactions in predictable ways. Our results suggest that the structure of species interactions in directionally structured ecosystems can be a key mediator of alterations to downstream habitats. Alterations to upstream habitats can thus cascade down to downstream communities, even without dispersal.

ecology↗