Vol.:(0123456789) 1 3 Neurochemical Research https://doi.org/10.1007/s11064-019-02861-x ORIGINAL PAPER CXCL1 and CXCL2 Inhibit the Axon Outgrowth in a Time‑ and Cell‑Type‑Dependent Manner in Adult Rat Dorsal Root Ganglia Neurons Antonia Teona Deftu 1  · Ruxandra Ciorescu 1  · Roxana‑Olimpia Gheorghe 1  · Dan Mihăilescu 1  · Violeta Ristoiu 1 Received: 10 May 2019 / Revised: 7 August 2019 / Accepted: 12 August 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The ability to regrow their axons after an injury is a hallmark of neurons in peripheral nervous system which distinguish them from central nervous system neurons. This ability is infuenced by their intrinsic capacity to regrow and by the extra- cellular environment which needs to be supportive of regrowth. CXCL1 [Chemokine (C-X-C motif) Ligand 1] and CXCL2 [Chemokine (C-X-C motif) Ligand 2] are two low-molecular-weight chemokines which can infuence neuronal proliferation, diferentiation and neurogenesis, but which are also upregulated by injury or infammation. In this study we investigated the efects of long-term incubation (24, 48 and 72 h) with diferent concentrations of CXCL1 (0.4, 4 or 40 nM) or CXCL2 (0.36, 3.6 or 36 nM) on the axon outgrowth of adult rat dorsal root ganglia neurons in culture. The results showed that both chemokines signifcantly inhibited the axon outgrowth, with large and medium NF200 (NeuroFilament 200) (+) dorsal root ganglia neurons afected quicker, compared to small IB4 (Isolectin B4) (+) dorsal root ganglia neurons which were afected after longer exposure. Blocking CXCR2 (C-X-C motif chemokine receptor 2) which mediates the efects of CXCL1 and CXCL2 prevented these efects, suggesting that CXCR2 may represent a new therapeutic target for promoting the axon outgrowth after a peripheral nerve injury. Keywords Chemokine (C-X-C motif) ligand 1 · Chemokine (C-X-C motif) ligand 2 · Axon growth · Dorsal root ganglia neurons Introduction After axotomy, neurons in the peripheral nervous system (PNS) are capable of regeneration [1], whereas neurons in the central nervous system (CNS) are generally not [2]. In addition in PNS, even though the axons regeneration can be quite precise [3], sometimes a loss of specifcity can occur [4] or the number of axons that reach their targets can be limited [5]. Therefore, understanding which factors can enhance or limit PNS regeneration is very important for developing therapies to treat nerve injury. Regeneration of axons in vivo is not cell autonomous, rather it is highly influenced by non-neuronal cells, in particular Schwann cells and macrophages [1]. Macrophages act not only locally at the lesion site where they are involved in Wallerian degeneration, but also distantly, at the DRG (dorsal root ganglia) level, where, through a number of secreted molecules they promote the expression of certain regeneration-associated genes in DRG neurons [6, 7]. CXCL1 [Chemokine (C-X-C motif) Ligand 1] and CXCL2 [Chemokine (C-X-C motif) Ligand 2] are two low-molecular-weight members of the ELR (Glu-Leu- Arg: the ELR motif) (+) CXC chemokine family with 78% homology of their sequence [8]. They are secreted by mac- rophages, but also by neutrophils, microglia, astrocytes or endothelial cells as response to injury or infammatory sig- nals [8, 9]. Interestingly, CXCL2 was also localized inside cortical neurons after a moderate lateral fuid percussion injury [ 10], which suggest a neuronal source for this chemokine, as well. Both of them are known to have pleio- tropic efects on neurons or immune cells, ranging from stimulating proliferation to increasing pain [11]. In par- ticular, CXCL2 has been shown to signifcantly increase * Violeta Ristoiu v_ristoiu@yahoo.com 1 Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, Sector 5, 050095 Bucharest, Romania