CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4⁺ and CD8⁺ lymphocytes, dendritic cells, eosinophils, macrophages, monocytes, and NK cells, as well in neoplasia. In this review, we discuss human CC motif chemokine ligands: CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 (CC motif chemokine receptor CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands). We present their functioning in human physiology and in neoplasia, including their role in the proliferation, apoptosis resistance, drug resistance, migration, and invasion of cancer cells. We discuss the significance of chemokine receptors in organ-specific metastasis, as well as the influence of each chemokine on the recruitment of various cells to the tumor niche, such as cancer-associated fibroblasts (CAF), Kupffer cells, myeloid-derived suppressor cells (MDSC), osteoclasts, tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and regulatory T cells (T_reg). Finally, we show how the effect of the chemokines on vascular endothelial cells and lymphatic endothelial cells leads to angiogenesis and lymphangiogenesis.

The human immune system is constantly exposed to xenobiotics and pathogens from the environment. Although the mechanisms underlying their influence have already been at least partially recognized, the effects of some factors, such as lead (Pb), still need to be clarified. The results of many studies indicate that Pb has a negative effect on the immune system, and in our review, we summarize the most recent evidence that Pb can promote inflammatory response. We also discuss possible molecular and biochemical mechanisms of its proinflammatory action, including the influence of Pb on cytokine metabolism (interleukins IL-2, IL-4, IL-8, IL-1b, IL-6), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α); the activity and expression of enzymes involved in the inflammatory process (cyclooxygenases); and the effect on selected acute phase proteins: C-reactive protein (CRP), haptoglobin, and ceruloplasmin. We also discuss the influence of Pb on the immune system cells (T and B lymphocytes, macrophages, Langerhans cells) and the secretion of IgA, IgE, IgG, histamine, and endothelin.

CXCL1 is one of the most important chemokines, part of a group of chemotactic cytokines involved in the development of many inflammatory diseases. It activates CXCR2 and, at high levels, CXCR1. The expression of CXCL1 is elevated in inflammatory reactions and also has important functions in physiology, including the induction of angiogenesis and recruitment of neutrophils. Due to a lack of reviews that precisely describe the regulation of CXCL1 expression and function, in this paper, we present the mechanisms of CXCL1 expression regulation with a special focus on cancer. We concentrate on the regulation of CXCL1 expression through the regulation of CXCL1 transcription and mRNA stability, including the involvement of NF-κB, p53, the effect of miRNAs and cytokines such as IFN-γ, IL-1β, IL-17, TGF-β and TNF-α. We also describe the mechanisms regulating CXCL1 activity in the extracellular space, including proteolytic processing, CXCL1 dimerization and the influence of the ACKR1/DARC receptor on CXCL1 localization. Finally, we explain the role of CXCL1 in cancer and possible therapeutic approaches directed against this chemokine.

This review describes the role of CXCL1, a chemokine crucial in inflammation as a chemoattractant for neutrophils, in physiology and in selected major non-cancer diseases. Due to the vast amount of available information, we focus on the role CXCL1 plays in the physiology of bones, bone marrow, muscle and the nervous system. For this reason, we describe its effects on hematopoietic stem cells, myoblasts, oligodendrocyte progenitors and osteoclast precursors. We also present the involvement of CXCL1 in diseases of selected tissues and organs including Alzheimer’s disease, epilepsy, herpes simplex virus type 1 (HSV-1) encephalitis, ischemic stroke, major depression, multiple sclerosis, neuromyelitis optica, neuropathic pain, osteoporosis, prion diseases, rheumatoid arthritis, tick-borne encephalitis (TBE), traumatic spinal cord injury and West Nile fever.

Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (T_reg), and tumor-associated macrophages (TAM) to a tumor niche.

C-X-C motif chemokine ligand 1 (CXCL1) is a member of the CXC chemokine subfamily and a ligand for CXCR2. Its main function in the immune system is the chemoattraction of neutrophils. However, there is a lack of comprehensive reviews summarizing the significance of CXCL1 in cancer processes. To fill this gap, this work describes the clinical significance and participation of CXCL1 in cancer processes in the most important reproductive cancers: breast cancer, cervical cancer, endometrial cancer, ovarian cancer, and prostate cancer. The focus is on both clinical aspects and the significance of CXCL1 in molecular cancer processes. We describe the association of CXCL1 with clinical features of tumors, including prognosis, ER, PR and HER2 status, and TNM stage. We present the molecular contribution of CXCL1 to chemoresistance and radioresistance in selected tumors and its influence on the proliferation, migration, and invasion of tumor cells. Additionally, we present the impact of CXCL1 on the microenvironment of reproductive cancers, including its effect on angiogenesis, recruitment, and function of cancer-associated cells (macrophages, neutrophils, MDSC, and T_reg). The article concludes by summarizing the significance of introducing drugs targeting CXCL1. This paper also discusses the significance of ACKR1/DARC in reproductive cancers.