How are MCPIP1 and cytokines mutually regulated in cancer-related immunity?

Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.

Chemokines and immunity / Quimiocinas e imunidade

Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity − members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family.

Quimiocinas são uma grande família de pequenas citocinas e seu peso molecular varia de 7 a 15kDa. As quimiocinas e seus receptores são capazes de controlar a migração e a residência de células imunes. Algumas quimiocinas são consideradas pró-inflamatórias e podem ser induzidas durante a resposta imune no sítio de infecção, enquanto outras são consideradas homeostáticas e estão envolvidas no controle da migração celular durante o desenvolvimento ou a manutenção dos tecidos. A importância fisiológica dessa família de mediadores é resultado de sua especificidade − os membros da família de quimiocinas induzem ao recrutamento de subtipos bem definidos de leucócitos. Existem duas grandes subfamílias de quimiocinas baseadas na posição dos resíduos de cisteínas: CXC e CC. Como regra geral, membros da família de quimiocinas CXC são quimiotáticos de neutrófilos, e as quimiocinas CC são quimiotáticos de monócitos e subtipos de linfócitos, apesar de existirem algumas exceções. Esta revisão discute o potencial papel das quimiocinas na inflamação focando nas duas quimiocinas mais bem caracterizadas: a proteína quimioatraente de monócitos-1, uma quimiocina CC, e a interleucina 8, uma quimiocina membro da subfamília CXC.