David Wilson Ferreira1, Cristina Ulecia-Morón2, Perla Abigail Alvarado-Vázquez3, Katharine Cunnane4, Carolina Moracho-Vilriales5, Rachel L Grosick6, Thiago Mattar Cunha7, E Alfonso Romero-Sandoval8. 1. Department of Pharmacology, University of São Paulo, Ribeirao Preto Medical School, 3900 Bandeirantes Ave., Ribeirão Preto, SP, 14049-900, Brazil; Department of Neurobiology, University of Pittsburgh School of Medicine, 3501 Fifth Ave - BST3, 6th floor, Pittsburgh, PA, 15260, USA. Electronic address: davidferreira_2005@hotmail.com. 2. Center for Biomedical Research Network on Mental Health (CIBERSAM), Avenida Monforte de Lemos, 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain; Department of Pharmacology and Toxicology, School of Medicine, and Instituto Universitario de Investigación en Neuroquímica (IUIN), Complutense University of Madrid, Avenida Complutense s/n., 28040, Madrid, Spain. Electronic address: cristinaulecia@gmail.com. 3. Department of Anesthesiology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA; Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Husargatan 3, Uppsala, 75123, Sweden. Electronic address: abigail1049@gmail.com. 4. Department of Anesthesiology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA. Electronic address: cunnka16@wfu.edu. 5. Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, 307 N Broad St., Clinton, SC, 29325, USA. Electronic address: carolinamoracho.3@gmail.com. 6. Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, 307 N Broad St., Clinton, SC, 29325, USA. Electronic address: rlgrosick@presby.edu. 7. Department of Pharmacology, University of São Paulo, Ribeirao Preto Medical School, 3900 Bandeirantes Ave., Ribeirão Preto, SP, 14049-900, Brazil. Electronic address: thicunha@usp.br. 8. Department of Anesthesiology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA. Electronic address: earomero.sandoval@gmail.com.
Abstract
Large tissue damage or wounds cause serious comorbidities and represent a major burden for patients, families, and health systems. Due to the pivotal role of immune cells in the proper resolution of inflammation and tissue repair, we focus our current study on the interaction of macrophages with skin cells, and specifically on the effects of CD163 gene induction in macrophages in wound healing. We hypothesize that the over-expression of the scavenger receptor gene CD163 in human macrophages would result in a more efficient wound healing process. Using 3D human wounded skin organotypic tissues, we observed that CD163 overexpression in THP-1 and human primary macrophages induced a more efficient re-epithelization when compared to control cells. Using human primary skin cells and an in vitro scratch assay we observed that CD163 overexpression in THP-1 macrophages promoted a more rapid and efficient wound healing process through a unique interaction with fibroblasts. The addition of CD163-blocking antibody, but not isotype control, blocked the efficient wound healing process induced by CD163 overexpression in macrophages. We found that the co-culture of skin cells and CD163 overexpressing macrophages reduced monocyte chemoattractant protein (MCP)-1 and enhanced tumor growth factor (TGF)-α, without altering interleukin (IL)-6 or TGF-β. Our findings show that CD163 induces a more efficient wound healing and seems to promote a wound milieu with a pro-resolution molecular profile. Our studies set the foundation to study this approach in in vivo clinically relevant settings to test its effects in wound healing processes such as acute major injuries, large surgeries, or chronic ulcers.
Large tissue damage or wounds cause serious comorbidities and represent a major burden for pan class="Species">patients, families, and health systems. Due to the pivotal role of immune cells in the propn>er resolution of pan class="Disease">inflammation and tissue repair, we focus our current study on the interaction of macrophages with skin cells, and specifically on the effects of CD163 gene induction in macrophages in wound healing. We hypothesize that the over-expression of the scavenger receptor gene CD163 in human macrophages would result in a more efficient wound healing process. Using 3D human wounded skin organotypic tissues, we observed that CD163 overexpression in THP-1 and human primary macrophages induced a more efficient re-epithelization when compared to control cells. Using human primary skin cells and an in vitro scratch assay we observed that CD163 overexpression in THP-1 macrophages promoted a more rapid and efficient wound healing process through a unique interaction with fibroblasts. The addition of CD163-blocking antibody, but not isotype control, blocked the efficient wound healing process induced by CD163 overexpression in macrophages. We found that the co-culture of skin cells and CD163 overexpressing macrophages reduced monocyte chemoattractant protein (MCP)-1 and enhanced tumor growth factor (TGF)-α, without altering interleukin (IL)-6 or TGF-β. Our findings show that CD163 induces a more efficient wound healing and seems to promote a wound milieu with a pro-resolution molecular profile. Our studies set the foundation to study this approach in in vivo clinically relevant settings to test its effects in wound healing processes such as acute major injuries, large surgeries, or chronic ulcers.