Although CD14 is expressed in most cells, its expression level is limited compared with that in MHC Ⅰ. The tissue-specific gene expression is determined by its chromatin structure and DNA methylation status. The restricted expression of CD14 is also determined by the specific combination of tissue-specific nuclear transcription factors or common nuclear transcription factors. For example, PU. 1 is only found in monocytes and B cells; NF-M (nuclear factor-M), found only in monocytes, is a member of the CAAT/enhancer binding protein (C/EBP) family; in addition, transcription factors such as Sp.1 (stimulatory protein 1) also participate in the regulation of gene expression. 

In the process of monocyte differentiation into macrophages, the expression of CD14 increased significantly. In order to study the regulation of the CD14 gene, Zhang et al. digested human chromosome 5 with Eco R Ⅰ and obtained the human CD14 gene after specific cloning of some gene fragments. The full length of the human CD14 gene contains a 5.5 kb coding sequence and a 4.2 kb upstream regulatory sequence at the 5 'end. At present, it is clear that a major transcription start site and a secondary transcription start site are located at 101 bp and 130 bp upstream of the ATG start site of the protein.

Compared with the non-mononuclear cell lines HeLa and REX, the human CD14 positive mononuclear cell line Mono Mac 6 contains a 128bp DNA fragment of the upstream sequence, which has a strong effect and monocyte-specific promoter activity. There are four regions in this fragment that can interact with nuclear proteins isolated from monocytes. The trans-acting factors binding to the GGGCGG frame are all named Sp (stimulatory protein). The cloned Sp.1 is composed of 696 amino acids and has three zinc finger structures at the N end, which is the binding site of DNA. Sp.1 can be combined into three different regions of CD14 promoter. Sp.1 is a zinc finger DNA-binding transcription factor, which can be detected in every mammalian cell, but its expression varies in different tissues.

Sp.1 is highly expressed in hematopoietic tissue, indicating that it plays an important role in the development of hematopoietic cells. It has been confirmed that Sp.1 is an important factor in regulating erythroid cells, lymphoid cells, and myeloid-specific genes. Sp.1 is not only a key factor for the tissue-specific expression of CD14 molecule in monocytes, but also involves the differentiation induction of CD14 expression, that is, promoting the differentiation of myeloid mononuclear stem cell lines. The regulation induced by vitamin D3 is mainly through the Sp.1 site to increase the expression of sCD14. Once the main binding site (- 110bp) of Sp.1 is mutated, it can reduce the activity of the tissue-specific promoters. These results and trans-activation experiments confirm that Sp.1 plays a key regulatory role in the expression of tissue-specific CD14 molecules in monocytes.

Another important transcription factor is the CCAAT/enhancer binding protein, which also plays an important role in regulating the activity of the CD14 promoters. CD14 mRNA can also be expressed in liver, lung, and kidney parenchyma cells stimulated by endotoxin, indicating that CD14 can also be synthesized and secreted in extramedullary cells. However, in the liver, the regulation mechanism of CD14 expression may be different from that of monocytes, and the liver is the main source of sCD14.