Regulatory Mechanisms and Chemical Signaling of Mediators Involved in the Inflammatory Phase of Cutaneous Wound Healing

Abstract

Wound healing is a highly complex biological process composed of three overlapping phases: inflammatory, proliferative, and remodeling. The acute inflammatory response has being an integral role in tissue healing and fundamental for the homeostasis and reestablishment. This phase depends on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events and complex interactions of the extracellular matrix, extracellular molecules, soluble mediators, various resident cells such as fibroblasts and keratinocytes, and infiltrated leukocyte subtypes that act to restore or replace the integrity of the skin. If this well-orchestrated response becomes deregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. In this chapter, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency in chronic inflammations, burns and hypertrophy.

Bicellular Tight Junctions and Wound Healing

“…Many cell types, including keratinocytes, epithelial cells, endothelial cells, fibroblasts, adipocytes; resident leukocytes, such as dendritic epidermal γδ T cells (DETCs), mast cells, and Langerhans cells; and infiltrating leukocytes, such as neutrophils, macrophages, and lymphocytes, including CD4/CD8 T cells, B cells, regulatory T cells, and natural killer T (NKT) cells; play pivotal roles in the wound healing process [10,11]. The migration, proliferation, and differentiation of these cells are tightly regulated by numerous factors, including inflammatory cytokines and chemokines, growth factors, proteinases, and hormones [10,11,12]. While it is known that TJs are present in several of these crucial cell populations and can regulate many of the cellular functions and interactions involved in wound healing, little work has been done to elucidate their specific contributions.…”

Cardiac Mast Cells: A Two-Head Regulator in Cardiac Homeostasis and Pathogenesis Following Injury

“…This may be related to some anti-inflammatory mediators secreted by CMCs, such as IL-10 and IL-13, which can limit the expansion of inflammatory response and protect non-infarcted cardiomyocytes. IL-10 restrains the inflammatory response by inhibiting the production of IL-1a, IL-1b, TNF-a, IL-6, and IL-8 through lipopolysaccharide-activated monocytes (91). This can be demonstrated by the obvious inflammatory response of IL-10 knockout mice after myocardial infarction, which is characterized by increased neutrophil infiltration and elevated blood TNF-a levels (92).…”